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Protein

Macrophage metalloelastase

Gene

Mmp12

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Calcium, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:97005. Mmp12.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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...)Sequence analysis1
Glycosylationi85N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi286 ↔ 473By similarity
Glycosylationi321N-linked (GlcNAc...)Sequence 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
Contains 4 hemopexin repeats.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
GeneTreeiENSGT00760000118870.
HOVERGENiHBG052484.
InParanoidiP34960.
KOiK01413.
OMAiGAYQLEY.
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.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR033739. M10A_MMP.
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]
PANTHERiPTHR10201:SF32. PTHR10201:SF32. 1 hit.
PfamiPF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFiPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSiPR00138. MATRIXIN.
SMARTiSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEiPS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP34960.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000005950.

Chemistry databases

BindingDBiP34960.
ChEMBLiCHEMBL2594.

Protein family/group databases

MEROPSiM10.009.
MoonProtiP34960.

PTM databases

iPTMnetiP34960.
PhosphoSitePlusiP34960.

Proteomic databases

MaxQBiP34960.
PaxDbiP34960.
PRIDEiP34960.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4321.
MGIiMGI:97005. Mmp12.

Phylogenomic databases

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
GeneTreeiENSGT00760000118870.
HOVERGENiHBG052484.
InParanoidiP34960.
KOiK01413.
OMAiGAYQLEY.
OrthoDBiEOG091G03DP.
PhylomeDBiP34960.
TreeFamiTF315428.

Enzyme and pathway databases

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

Miscellaneous databases

PROiP34960.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000049723.
CleanExiMM_MME.
MM_MMP12.
ExpressionAtlasiP34960. baseline and differential.
GenevisibleiP34960. MM.

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.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR033739. M10A_MMP.
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]
PANTHERiPTHR10201:SF32. PTHR10201:SF32. 1 hit.
PfamiPF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFiPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSiPR00138. MATRIXIN.
SMARTiSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEiPS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

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 historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: July 10, 2007
Last modified: November 30, 2016
This is version 157 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.