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Protein

Macrophage metalloelastase

Gene

Mmp12

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

Catalytic activityi

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.

Cofactori

Protein has several cofactor binding sites:
  • Ca2+By similarityNote: Binds 4 Ca2+ ions per subunit.By similarity
  • Zn2+By similarityNote: Binds 2 Zn2+ ions per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi96Zinc 2; in inhibited formBy similarity1
Metal bindingi128Calcium 1By similarity1
Metal bindingi162Calcium 2By similarity1
Metal bindingi172Zinc 1By similarity1
Metal bindingi174Zinc 1By similarity1
Metal bindingi179Calcium 3By similarity1
Metal bindingi180Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi182Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi184Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi187Zinc 1By similarity1
Metal bindingi194Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi198Calcium 2By similarity1
Metal bindingi200Zinc 1By similarity1
Metal bindingi202Calcium 3By similarity1
Metal bindingi203Calcium 1By similarity1
Metal bindingi205Calcium 1By similarity1
Metal bindingi205Calcium 3By similarity1
Metal bindingi222Zinc 2; catalyticBy similarity1
Active sitei223PROSITE-ProRule annotation1
Metal bindingi226Zinc 2; catalyticBy similarity1
Metal bindingi232Zinc 2; catalyticBy similarity1
Metal bindingi293Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi385Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi434Calcium 4; via carbonyl oxygenBy similarity1

GO - Molecular functioni

GO - Biological processi

  • cellular response to virus Source: CAFA
  • negative regulation of transcription by RNA polymerase II Source: CAFA
  • negative regulation of type I interferon-mediated signaling pathway Source: CAFA
  • positive regulation of epithelial cell proliferation involved in wound healing Source: MGI
  • positive regulation of gene expression Source: CAFA
  • positive regulation of interferon-alpha secretion Source: CAFA
  • positive regulation of transcription by RNA polymerase II Source: MGI
  • positive regulation of type I interferon-mediated signaling pathway Source: CAFA
  • protein import into nucleus Source: CAFA
  • proteolysis Source: MGI
  • regulation of defense response to virus by host Source: CAFA
  • wound healing, spreading of epidermal cells Source: MGI

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-1442490 Collagen degradation
R-MMU-1474228 Degradation of the extracellular matrix

Protein family/group databases

MEROPSiM10.009
MoonProtiP34960

Names & Taxonomyi

Protein namesi
Recommended name:
Macrophage metalloelastase (EC:3.4.24.65)
Short name:
MME
Alternative name(s):
Matrix metalloproteinase-12
Short name:
MMP-12
Gene namesi
Name:Mmp12
Synonyms:Mme, Mmel
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:97005 Mmp12

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2594

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28CuratedAdd BLAST28
PropeptideiPRO_000002877829 – 109Activation peptide1 PublicationAdd BLAST81
ChainiPRO_0000028779110 – 473Macrophage metalloelastaseAdd BLAST364

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi32N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi85N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi286 ↔ 473By similarity
Glycosylationi321N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

MaxQBiP34960
PaxDbiP34960
PRIDEiP34960

PTM databases

iPTMnetiP34960
PhosphoSitePlusiP34960

Expressioni

Gene expression databases

BgeeiENSMUSG00000049723
CleanExiMM_MME
MM_MMP12
ExpressionAtlasiP34960 baseline and differential
GenevisibleiP34960 MM

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000005950

Chemistry databases

BindingDBiP34960

Structurei

3D structure databases

ProteinModelPortaliP34960
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati289 – 332Hemopexin 1Add BLAST44
Repeati333 – 379Hemopexin 2Add BLAST47
Repeati381 – 429Hemopexin 3Add BLAST49
Repeati430 – 473Hemopexin 4Add BLAST44

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi94 – 101Cysteine switchBy similarity8

Domaini

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 similaritiesi

Belongs to the peptidase M10A family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG1565 Eukaryota
ENOG410XQ5D LUCA
GeneTreeiENSGT00760000118870
HOVERGENiHBG052484
InParanoidiP34960
KOiK01413
OMAiFLFKDDK
OrthoDBiEOG091G03DP
PhylomeDBiP34960
TreeFamiTF315428

Family and domain databases

CDDicd00094 HX, 1 hit
cd04278 ZnMc_MMP, 1 hit
Gene3Di2.110.10.10, 1 hit
3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR000585 Hemopexin-like_dom
IPR036375 Hemopexin-like_dom_sf
IPR018487 Hemopexin-like_repeat
IPR018486 Hemopexin_CS
IPR033739 M10A_MMP
IPR024079 MetalloPept_cat_dom_sf
IPR028718 MMP12
IPR001818 Pept_M10_metallopeptidase
IPR021190 Pept_M10A
IPR021158 Pept_M10A_Zn_BS
IPR006026 Peptidase_Metallo
IPR002477 Peptidoglycan-bd-like
IPR036365 PGBD-like_sf
PANTHERiPTHR10201:SF32 PTHR10201:SF32, 1 hit
PfamiView protein in Pfam
PF00045 Hemopexin, 4 hits
PF00413 Peptidase_M10, 1 hit
PF01471 PG_binding_1, 1 hit
PIRSFiPIRSF001191 Peptidase_M10A_matrix, 1 hit
PRINTSiPR00138 MATRIXIN
SMARTiView protein in SMART
SM00120 HX, 4 hits
SM00235 ZnMc, 1 hit
SUPFAMiSSF47090 SSF47090, 1 hit
SSF50923 SSF50923, 1 hit
PROSITEiView protein in PROSITE
PS00546 CYSTEINE_SWITCH, 1 hit
PS00024 HEMOPEXIN, 1 hit
PS51642 HEMOPEXIN_2, 4 hits
PS00142 ZINC_PROTEASE, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P34960-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSCTLLKGVC TMKFLMMIVF LQVSACGAAP MNDSEFAEWY LSRFYDYGKD
60 70 80 90 100
RIPMTKTKTN RNFLKEKLQE MQQFFGLEAT GQLDNSTLAI MHIPRCGVPD
110 120 130 140 150
VQHLRAVPQR SRWMKRYLTY RIYNYTPDMK REDVDYIFQK AFQVWSDVTP
160 170 180 190 200
LRFRKLHKDE ADIMILFAFG AHGDFNYFDG KGGTLAHAFY PGPGIQGDAH
210 220 230 240 250
FDEAETWTKS FQGTNLFLVA VHELGHSLGL QHSNNPKSIM YPTYRYLNPS
260 270 280 290 300
TFRLSADDIR NIQSLYGAPV KPPSLTKPSS PPSTFCHQSL SFDAVTTVGE
310 320 330 340 350
KIFFFKDWFF WWKLPGSPAT NITSISSIWP SIPSGIQAAY EIESRNQLFL
360 370 380 390 400
FKDEKYWLIN NLVPEPHYPR SIYSLGFSAS VKKVDAAVFD PLRQKVYFFV
410 420 430 440 450
DKHYWRYDVR QELMDPAYPK LISTHFPGIK PKIDAVLYFK RHYYIFQGAY
460 470
QLEYDPLFRR VTKTLKSTSW FGC
Length:473
Mass (Da):54,971
Last modified:July 10, 2007 - v3
Checksum:iD377250610BA249E
GO

Sequence cautioni

The sequence AAA39526 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC40889 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti65K → E in AAH19135 (PubMed:15489334).Curated1
Sequence conflicti65K → E in CAJ18584 (Ref. 4) Curated1
Sequence conflicti78E → V in BAE30809 (PubMed:16141072).Curated1
Sequence conflicti78E → V in BAE30260 (PubMed:16141072).Curated1
Sequence conflicti78E → V in BAE30039 (PubMed:16141072).Curated1
Sequence conflicti78E → V in BAE29689 (PubMed:16141072).Curated1
Sequence conflicti80T → N in BAE33415 (PubMed:16141072).Curated1
Sequence conflicti87T → A in BAE42486 (PubMed:16141072).Curated1
Sequence conflicti172H → N in BAE42198 (PubMed:16141072).Curated1
Sequence conflicti188A → V in AAA39526 (PubMed:1537850).Curated1
Sequence conflicti199A → T in BAC40836 (PubMed:16141072).Curated1
Sequence conflicti241Y → D in AAH19135 (PubMed:15489334).Curated1
Sequence conflicti241Y → D in CAJ18584 (Ref. 4) Curated1
Sequence conflicti247L → F in BAE33072 (PubMed:16141072).Curated1
Sequence conflicti250S → N in AAH19135 (PubMed:15489334).Curated1
Sequence conflicti250S → N in CAJ18584 (Ref. 4) Curated1
Sequence conflicti268A → P in BAC40846 (PubMed:16141072).Curated1
Sequence conflicti272P → T in AAH19135 (PubMed:15489334).Curated1
Sequence conflicti272P → T in CAJ18584 (Ref. 4) Curated1
Sequence conflicti303F → L in AAA39526 (PubMed:1537850).Curated1
Sequence conflicti303F → Y in BAC40889 (PubMed:16141072).Curated1
Sequence conflicti303F → Y in BAC40913 (PubMed:16141072).Curated1
Sequence conflicti319A → D in BAE33415 (PubMed:16141072).Curated1
Sequence conflicti323T → I in AAH19135 (PubMed:15489334).Curated1
Sequence conflicti323T → I in CAJ18584 (Ref. 4) Curated1
Sequence conflicti328I → T in BAE41743 (PubMed:16141072).Curated1
Sequence conflicti335G → A in AAA39526 (PubMed:1537850).Curated1
Sequence conflicti403H → Q in AAH19135 (PubMed:15489334).Curated1
Sequence conflicti403H → Q in CAJ18584 (Ref. 4) Curated1
Sequence conflicti432K → R in BAC40836 (PubMed:16141072).Curated1
Sequence conflicti467S → G in BAE42201 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M82831 mRNA Translation: AAA39526.1 Different initiation.
AK089309 mRNA Translation: BAC40836.1
AK089335 mRNA Translation: BAC40846.1
AK089452 mRNA Translation: BAC40889.1 Different initiation.
AK089523 mRNA Translation: BAC40913.1
AK090051 mRNA Translation: BAC41067.1
AK150596 mRNA Translation: BAE29689.1
AK151021 mRNA Translation: BAE30039.1
AK151273 mRNA Translation: BAE30260.1
AK151933 mRNA Translation: BAE30809.1
AK155139 mRNA Translation: BAE33072.1
AK155743 mRNA Translation: BAE33411.1
AK155747 mRNA Translation: BAE33414.1
AK155748 mRNA Translation: BAE33415.1
AK155865 mRNA Translation: BAE33469.1
AK170360 mRNA Translation: BAE41743.1
AK170364 mRNA Translation: BAE41746.1
AK170798 mRNA Translation: BAE42035.1
AK170804 mRNA Translation: BAE42039.1
AK170976 mRNA Translation: BAE42154.1
AK171006 mRNA Translation: BAE42177.1
AK171032 mRNA Translation: BAE42198.1
AK171036 mRNA Translation: BAE42201.1
AK171176 mRNA Translation: BAE42294.1
AK171428 mRNA Translation: BAE42446.1
AK171447 mRNA Translation: BAE42457.1
AK171448 mRNA Translation: BAE42458.1
AK171449 mRNA Translation: BAE42459.1
AK171450 mRNA Translation: BAE42460.1
AK171466 mRNA Translation: BAE42472.1
AK171468 mRNA Translation: BAE42474.1
AK171470 mRNA Translation: BAE42476.1
AK171472 mRNA Translation: BAE42478.1
AK171485 mRNA Translation: BAE42486.1
AK171518 mRNA Translation: BAE42502.1
AK171542 mRNA Translation: BAE42516.1
AK171570 mRNA Translation: BAE42531.1
BC019135 mRNA Translation: AAH19135.2
CT010377 mRNA Translation: CAJ18584.1
CCDSiCCDS22804.1
PIRiA42401
RefSeqiNP_001307005.1, NM_001320076.1
NP_001307006.1, NM_001320077.1
NP_032631.3, NM_008605.3
UniGeneiMm.2055

Genome annotation databases

EnsembliENSMUST00000005950; ENSMUSP00000005950; ENSMUSG00000049723
GeneIDi17381
KEGGimmu:17381
UCSCiuc009och.1 mouse

Similar proteinsi

Entry informationi

Entry nameiMMP12_MOUSE
AccessioniPrimary (citable) accession number: P34960
Secondary accession number(s): Q3TB28
, Q3TBV6, Q3TBV9, Q3TD61, Q3U1S8, Q3U1S9, Q3U2R8, Q3UBC5, Q4FJM7, Q8BJ92, Q8BJB3, Q8BJB6, Q8BJB8, Q8BJB9, Q8VED6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: July 10, 2007
Last modified: March 28, 2018
This is version 166 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health