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Q99542 (MMP19_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Matrix metalloproteinase-19

Short name=MMP-19
EC=3.4.24.-
Alternative name(s):
Matrix metalloproteinase RASI
Matrix metalloproteinase-18
Short name=MMP-18
Gene names
Name:MMP19
Synonyms:MMP18, RASI
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length508 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Endopeptidase that degrades various components of the extracellular matrix, such as aggrecan and cartilage oligomeric matrix protein (comp), during development, haemostasis and pathological conditions (arthritic disease). May also play a role in neovascularization or angiogenesis. Hydrolyzes collagen type IV, laminin, nidogen, nascin-C isoform, fibronectin, and type I gelatin. Ref.8 Ref.9

Catalytic activity

Cleaves aggrecan at the 360-Ser-|-Phe-361 site.

Cofactor

Binds 1 zinc ion per subunit By similarity.

Calcium By similarity.

Enzyme regulation

Strongly inhibited by TIMP-2, TIMP-3 and TIMP-4, while TIMP-1 is less efficient.

Subcellular location

Secretedextracellular spaceextracellular matrix By similarity.

Tissue specificity

Expressed in mammary gland, placenta, lung, pancreas, ovary, small intestine, spleen, thymus, prostate, testis colon, heart and blood vessel walls. Not detected in brain and peripheral blood leukocytes. Also expressed in the synovial fluid of normal and rheumatoid patients.

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.

Post-translational modification

Activated by autolytic cleavage after Lys-97.

Involvement in disease

May play a role in pathological processes participating in rheumatoid arthritis (RA)-associated joint tissue destruction. Autoantigen anti-MMP19 are frequent in RA patients.

Sequence similarities

Belongs to the peptidase M10A family.

Contains 4 hemopexin repeats.

Sequence caution

The sequence AAC99995.1 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.

Ontologies

Keywords
   Biological processAngiogenesis
Collagen degradation
Differentiation
   Cellular componentExtracellular matrix
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
Signal
   LigandCalcium
Metal-binding
Zinc
   Molecular functionDevelopmental protein
Hydrolase
Metalloprotease
Protease
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

collagen catabolic process

Traceable author statement. Source: Reactome

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

luteolysis

Inferred from electronic annotation. Source: Ensembl

ovarian follicle development

Inferred from electronic annotation. Source: Ensembl

ovulation from ovarian follicle

Inferred from electronic annotation. Source: Ensembl

proteolysis

Non-traceable author statement Ref.2. Source: UniProtKB

response to cAMP

Inferred from electronic annotation. Source: Ensembl

response to hormone

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

proteinaceous extracellular matrix

Non-traceable author statement Ref.8. Source: UniProtKB

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

metalloendopeptidase activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q99542-1)

Also known as: RASI-1; RASI-11;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q99542-3)

Also known as: RASI-9;

The sequence of this isoform differs from the canonical sequence as follows:
     1-286: Missing.
     287-298: DPCSSELDAMML → MGVTWDFSMSNG
Isoform 3 (identifier: Q99542-4)

Also known as: RASI-6;

The sequence of this isoform differs from the canonical sequence as follows:
     58-63: RAFQEA → SLRSAG
     64-508: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Propeptide19 – 9779
PRO_0000028826
Chain98 – 508411Matrix metalloproteinase-19
PRO_0000028827

Regions

Repeat286 – 33348Hemopexin 1
Repeat334 – 38047Hemopexin 2
Repeat381 – 42545Hemopexin 3
Repeat426 – 47247Hemopexin 4
Motif83 – 908Cysteine switch By similarity
Compositional bias265 – 2717Poly-Glu

Sites

Active site2131 By similarity
Metal binding851Zinc; in inhibited form By similarity
Metal binding2121Zinc; catalytic By similarity
Metal binding2161Zinc; catalytic By similarity
Metal binding2221Zinc; catalytic By similarity

Amino acid modifications

Glycosylation4641N-linked (GlcNAc...) Potential
Disulfide bond289 ↔ 472 By similarity

Natural variations

Alternative sequence1 – 286286Missing in isoform 2.
VSP_005457
Alternative sequence58 – 636RAFQEA → SLRSAG in isoform 3.
VSP_041893
Alternative sequence64 – 508445Missing in isoform 3.
VSP_041894
Alternative sequence287 – 29812DPCSS…DAMML → MGVTWDFSMSNG in isoform 2.
VSP_005458
Natural variant1031R → C. Ref.6
Corresponds to variant rs17844794 [ dbSNP | Ensembl ].
VAR_021036
Natural variant2451P → S.
Corresponds to variant rs1056784 [ dbSNP | Ensembl ].
VAR_054006
Natural variant4881P → T. Ref.6
Corresponds to variant rs17118042 [ dbSNP | Ensembl ].
VAR_021037
Natural variant4911T → M. Ref.6
Corresponds to variant rs17844806 [ dbSNP | Ensembl ].
VAR_021038

Experimental info

Mutagenesis881E → P: Reduced autolysis rate.
Mutagenesis901P → V: Reduced autolysis rate.
Sequence conflict3761V → S in CAA69913. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (RASI-1) (RASI-11) [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: BA480549AA9A8972

FASTA50857,357
        10         20         30         40         50         60 
MNCQQLWLGF LLPMTVSGRV LGLAEVAPVD YLSQYGYLQK PLEGSNNFKP EDITEALRAF 

        70         80         90        100        110        120 
QEASELPVSG QLDDATRARM RQPRCGLEDP FNQKTLKYLL LGRWRKKHLT FRILNLPSTL 

       130        140        150        160        170        180 
PPHTARAALR QAFQDWSNVA PLTFQEVQAG AADIRLSFHG RQSSYCSNTF DGPGRVLAHA 

       190        200        210        220        230        240 
DIPELGSVHF DEDEFWTEGT YRGVNLRIIA AHEVGHALGL GHSRYSQALM APVYEGYRPH 

       250        260        270        280        290        300 
FKLHPDDVAG IQALYGKKSP VIRDEEEEET ELPTVPPVPT EPSPMPDPCS SELDAMMLGP 

       310        320        330        340        350        360 
RGKTYAFKGD YVWTVSDSGP GPLFRVSALW EGLPGNLDAA VYSPRTQWIH FFKGDKVWRY 

       370        380        390        400        410        420 
INFKMSPGFP KKLNRVEPNL DAALYWPLNQ KVFLFKGSGY WQWDELARTD FSSYPKPIKG 

       430        440        450        460        470        480 
LFTGVPNQPS AAMSWQDGRV YFFKGKVYWR LNQQLRVEKG YPRNISHNWM HCRPRTIDTT 

       490        500 
PSGGNTTPSG TGITLDTTLS ATETTFEY 

« Hide

Isoform 2 (RASI-9) [UniParc].

Checksum: 594DBE2F520DC0FE
Show »

FASTA22225,350
Isoform 3 (RASI-6) [UniParc].

Checksum: C134E217099633E8
Show »

FASTA636,931

References

« Hide 'large scale' references
[1]"Identification of MMP-18, a putative novel human matrix metalloproteinase."
Cossins J., Dudgeon T.J., Catlin G., Gearing A.J.H., Clements J.M.
Biochem. Biophys. Res. Commun. 228:494-498(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Mammary gland.
[2]"Identification and characterization of a novel human matrix metalloproteinase with unique structural characteristics, chromosomal location and tissue distribution."
Pendas A.M., Knaeuper V.V., Puente X.S., Llano E., Mattei M.-G., Apte S., Murphy G., Lopez-Otin C.
J. Biol. Chem. 272:4281-4286(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[3]"The matrix metalloproteinase RASI-1 is expressed in synovial blood vessels of a rheumatoid arthritis patient."
Kolb C., Mauch S., Peter H.-H., Krawinkel U., Sedlacek R.
Immunol. Lett. 57:83-88(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Rheumatoid arthritic synovial fluid.
[4]"Matrix metalloproteinase MMP-19 (RASI-1) is expressed on the surface of activated peripheral blood mononuclear cells and is detected as an autoantigen in rheumatoid arthritis."
Sedlacek R., Mauch S., Kolb B., Schaetzlein C., Eibel H., Peter H.-H., Schmitt J., Krawinkel U.
Immunobiology 198:408-423(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Rheumatoid arthritic synovial fluid.
[5]Mauch S., Sedlacek R., Krawinkel U., Schaetzlein C.
Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
[6]NIEHS SNPs program
Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-103; THR-488 AND MET-491.
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]"Biochemical characterization of the catalytic domain of human matrix metalloproteinase 19. Evidence for a role as a potent basement membrane degrading enzyme."
Stracke J.O., Hutton M., Stewart M., Pendas A.M., Smith B., Lopez-Otin C., Murphy G., Knaeuper V.
J. Biol. Chem. 275:14809-14816(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, MUTAGENESIS.
[9]"Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP)."
Stracke J.O., Fosang A.J., Last K., Mercuri F.A., Pendas A.M., Llano E., Perris R., Di Cesare P.E., Murphy G., Knaeuper V.
FEBS Lett. 478:52-56(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y08622 mRNA. Translation: CAA69913.1.
X92521 mRNA. Translation: CAA63299.1.
U37791 mRNA. Translation: AAC51521.1.
U38321 mRNA. Translation: AAB63008.1.
U38431 mRNA. Translation: AAC99995.1. Sequence problems.
U38322 mRNA. Translation: AAB63009.1.
AY706993 Genomic DNA. Translation: AAT97983.1.
BC050368 mRNA. Translation: AAH50368.1.
PIRJC5082.
RefSeqNP_001259030.1. NM_001272101.1.
NP_002420.1. NM_002429.5.
UniGeneHs.591033.

3D structure databases

ProteinModelPortalQ99542.
SMRQ99542. Positions 38-456.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ99542. 1 interaction.
STRING9606.ENSP00000313437.

Chemistry

BindingDBQ99542.
ChEMBLCHEMBL1938214.

Protein family/group databases

MEROPSM10.021.

PTM databases

PhosphoSiteQ99542.

Polymorphism databases

DMDM12643345.

Proteomic databases

PaxDbQ99542.
PRIDEQ99542.

Protocols and materials databases

DNASU4327.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000322569; ENSP00000313437; ENSG00000123342. [Q99542-1]
ENST00000394182; ENSP00000377736; ENSG00000123342. [Q99542-3]
ENST00000552872; ENSP00000446776; ENSG00000123342. [Q99542-4]
GeneID4327.
KEGGhsa:4327.
UCSCuc001sia.3. human. [Q99542-3]
uc001sib.4. human. [Q99542-1]

Organism-specific databases

CTD4327.
GeneCardsGC12M056230.
HGNCHGNC:7165. MMP19.
HPAHPA012845.
MIM601807. gene.
neXtProtNX_Q99542.
PharmGKBPA30876.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG295915.
HOGENOMHOG000217927.
HOVERGENHBG052484.
InParanoidQ99542.
KOK07998.
OMAWMHCHPQ.
PhylomeDBQ99542.
TreeFamTF315428.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.
REACT_150387. Gelatin degradation by MMP19.

Gene expression databases

ArrayExpressQ99542.
BgeeQ99542.
CleanExHS_MMP19.
GenevestigatorQ99542.

Family and domain databases

Gene3D1.10.101.10. 1 hit.
2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR024079. MetalloPept_cat_dom.
IPR028724. MMP19.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERPTHR10201. PTHR10201. 1 hit.
PTHR10201:SF18. PTHR10201:SF18. 1 hit.
PfamPF00045. Hemopexin. 3 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.
PROSITEPS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMMP19.
GenomeRNAi4327.
NextBio17029.
PROQ99542.
SOURCESearch...

Entry information

Entry nameMMP19_HUMAN
AccessionPrimary (citable) accession number: Q99542
Secondary accession number(s): O15278, O95606, Q99580
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: May 1, 1997
Last modified: April 16, 2014
This is version 149 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

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 12

Human chromosome 12: entries, gene names and cross-references to MIM