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P39900 (MMP12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Macrophage metalloelastase

Short name=MME
EC=3.4.24.65
Alternative name(s):
Macrophage elastase
Short name=ME
Short name=hME
Matrix metalloproteinase-12
Short name=MMP-12
Gene names
Name:MMP12
Synonyms:HME
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length470 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (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.

Binds 2 zinc ions per subunit.

Subcellular location

Secretedextracellular spaceextracellular matrix Probable.

Tissue specificity

Found in alveolar macrophages but not in peripheral blood monocytes.

Induction

By exposure to bacterial lipopolysaccharides (LPS). 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.

Sequence similarities

Belongs to the peptidase M10A family.

Contains 4 hemopexin repeats.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1616 Probable
Propeptide17 – 10589Activation peptide By similarity
PRO_0000028776
Chain106 – 470365Macrophage metalloelastase
PRO_0000028777

Regions

Repeat279 – 32850Hemopexin 1
Repeat329 – 37547Hemopexin 2
Repeat377 – 42549Hemopexin 3
Repeat426 – 47045Hemopexin 4
Motif90 – 978Cysteine switch By similarity

Sites

Active site2191
Metal binding921Zinc 2; in inhibited form By similarity
Metal binding1241Calcium 1
Metal binding1581Calcium 2
Metal binding1681Zinc 1
Metal binding1701Zinc 1
Metal binding1751Calcium 3
Metal binding1761Calcium 3; via carbonyl oxygen
Metal binding1781Calcium 3; via carbonyl oxygen
Metal binding1801Calcium 3; via carbonyl oxygen
Metal binding1831Zinc 1
Metal binding1901Calcium 2; via carbonyl oxygen
Metal binding1921Calcium 2; via carbonyl oxygen
Metal binding1941Calcium 2
Metal binding1961Zinc 1
Metal binding1981Calcium 3
Metal binding1991Calcium 1
Metal binding2011Calcium 1
Metal binding2011Calcium 3
Metal binding2181Zinc 2; catalytic
Metal binding2221Zinc 2; catalytic
Metal binding2281Zinc 2; catalytic
Metal binding2891Calcium 4; via carbonyl oxygen By similarity
Metal binding3331Calcium 4; via carbonyl oxygen By similarity
Metal binding3811Calcium 4; via carbonyl oxygen By similarity
Metal binding4301Calcium 4; via carbonyl oxygen By similarity

Amino acid modifications

Glycosylation201N-linked (GlcNAc...) Potential
Glycosylation2851N-linked (GlcNAc...) Potential
Disulfide bond282 ↔ 470 By similarity

Natural variations

Natural variant3571N → S. Ref.2 Ref.5
Corresponds to variant rs652438 [ dbSNP | Ensembl ].
VAR_021343
Natural variant4691G → R. Ref.2
Corresponds to variant rs28381701 [ dbSNP | Ensembl ].
VAR_021344

Secondary structure

................................................................................... 470
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P39900 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 8C745EEA8C0EA216

FASTA47054,002
        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 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages."
Shapiro S.D., Kobayashi D.K., Ley T.J.
J. Biol. Chem. 268:23824-23829(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Alveolar macrophage.
[2]NIEHS SNPs program
Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-357 AND ARG-469.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Esophagus.
[4]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. expand/collapse author list , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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], VARIANT SER-357.
[6]"Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase."
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.
J. Biol. Chem. 272:12189-12194(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[7]"Substrate specificity determinants of human macrophage elastase (MMP-12) based on the 1.1 A crystal structure."
Lang R., Kocourek A., Braun M., Tschesche H., Huber R., Bode W., Maskos K.
J. Mol. Biol. 312:731-742(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.09 ANGSTROMS) OF 106-263.
[8]"Crystal structure of human macrophage elastase (MMP-12) in complex with a hydroxamic acid inhibitor."
Nar H., Werle K., Bauer M.M.T., Dollinger H., Jung B.
J. Mol. Biol. 312:743-751(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 100-280.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L23808 mRNA. Translation: AAA58658.1. Sequence problems.
AY856072 Genomic DNA. Translation: AAW29944.1.
AK313959 mRNA. Translation: BAG36675.1.
CH471065 Genomic DNA. Translation: EAW67033.1.
BC112301 mRNA. Translation: AAI12302.1.
BC143773 mRNA. Translation: AAI43774.1.
PIRA49499.
RefSeqNP_002417.2. NM_002426.4.
UniGeneHs.1695.
Hs.709832.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1JIZX-ray2.60A/B100-264[»]
1JK3X-ray1.09A106-263[»]
1OS2X-ray2.15A/B/C/D/E/F106-268[»]
1OS9X-ray1.85A/B/C/D/E/F106-268[»]
1RMZX-ray1.34A106-263[»]
1ROSX-ray2.00A/B106-268[»]
1UTTX-ray2.20A106-264[»]
1UTZX-ray2.50A/B106-264[»]
1Y93X-ray1.03A106-263[»]
1YCMNMR-A106-263[»]
1Z3JNMR-A106-263[»]
2HU6X-ray1.32A106-263[»]
2JXYNMR-A278-470[»]
2K2GNMR-A100-263[»]
2K9CNMR-A112-263[»]
2KRJNMR-A112-263[»]
2OXUX-ray1.24A106-263[»]
2OXWX-ray1.15A106-263[»]
2OXZX-ray1.90A106-263[»]
2POJNMR-A100-263[»]
2W0DX-ray2.00A/B/C/D106-263[»]
2WO8X-ray2.00A/B/C/D106-268[»]
2WO9X-ray1.70A/B/C/D106-268[»]
2WOAX-ray2.30A/B/C/D106-268[»]
2Z2DNMR-A100-263[»]
3BA0X-ray3.00A106-470[»]
3EHXX-ray1.90A106-263[»]
3EHYX-ray1.90A106-263[»]
3F15X-ray1.70A106-263[»]
3F16X-ray1.16A106-263[»]
3F17X-ray1.10A106-263[»]
3F18X-ray1.13A106-263[»]
3F19X-ray1.13A106-263[»]
3F1AX-ray1.25A106-263[»]
3LIKX-ray1.80A106-263[»]
3LILX-ray1.80A106-263[»]
3LIRX-ray1.90A106-263[»]
3LJGX-ray1.31A106-263[»]
3LK8X-ray1.80A106-263[»]
3LKAX-ray1.80A106-263[»]
3N2UX-ray1.81A106-263[»]
3N2VX-ray1.55A106-263[»]
3NX7X-ray1.80A106-263[»]
3RTSX-ray1.81A106-263[»]
3RTTX-ray1.82A106-263[»]
3TS4X-ray1.59A106-263[»]
3TSKX-ray2.00A106-263[»]
3UVCX-ray1.30A/B106-263[»]
4EFSX-ray1.63A106-263[»]
4GQLX-ray1.15A106-263[»]
4GR0X-ray1.50A106-263[»]
4GR3X-ray1.49A106-263[»]
4GR8X-ray1.30A111-262[»]
4GUYX-ray2.00A106-263[»]
4H30X-ray1.43A/B106-263[»]
4H49X-ray2.16A/B/C/D106-263[»]
4H76X-ray1.50A106-263[»]
4H84X-ray1.59A/B106-263[»]
4I03X-ray1.70A106-263[»]
4IJOX-ray1.90A106-263[»]
DisProtDP00571.
ProteinModelPortalP39900.
SMRP39900. Positions 34-470.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110464. 1 interaction.
IntActP39900. 1 interaction.
MINTMINT-7709562.
STRING9606.ENSP00000320664.

Chemistry

BindingDBP39900.
ChEMBLCHEMBL4393.
DrugBankDB00551. Acetohydroxamic Acid.

Protein family/group databases

MEROPSM10.009.

PTM databases

PhosphoSiteP39900.

Polymorphism databases

DMDM729179.

Proteomic databases

PaxDbP39900.
PRIDEP39900.

Protocols and materials databases

DNASU4321.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000571244; ENSP00000458585; ENSG00000262406.
GeneID4321.
KEGGhsa:4321.
UCSCuc001phk.3. human.

Organism-specific databases

CTD4321.
GeneCardsGC11M102767.
HGNCHGNC:7158. MMP12.
MIM601046. gene.
neXtProtNX_P39900.
PharmGKBPA30870.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG323958.
HOGENOMHOG000217927.
HOVERGENHBG052484.
InParanoidP39900.
KOK01413.
OMARKHYITY.
OrthoDBEOG7XPZ57.
PhylomeDBP39900.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

CleanExHS_MMP12.
GenevestigatorP39900.

Family and domain databases

Gene3D2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR024079. MetalloPept_cat_dom.
IPR028718. MMP12.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR021158. Pept_M10A_Zn_BS.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERPTHR10201:SF32. PTHR10201:SF32. 1 hit.
PfamPF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSPR00138. MATRIXIN.
SMARTSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEPS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMMP12. human.
EvolutionaryTraceP39900.
GeneWikiMatrix_metallopeptidase_12.
GenomeRNAi4321.
NextBio17001.
PROP39900.
SOURCESearch...

Entry information

Entry nameMMP12_HUMAN
AccessionPrimary (citable) accession number: P39900
Secondary accession number(s): B2R9X8, B7ZLF6, Q2M1L9
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: June 11, 2014
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM