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Protein

Matrix metalloproteinase-19

Gene

MMP19

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
  • Ca2+By similarity

Enzyme regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi85Zinc; in inhibited formBy similarity1
Metal bindingi212Zinc; catalyticPROSITE-ProRule annotation1
Active sitei213PROSITE-ProRule annotation1
Metal bindingi216Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi222Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Angiogenesis, Collagen degradation, Differentiation

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000123342-MONOMER.
ReactomeiR-HSA-1442490. Collagen degradation.
R-HSA-1474228. Degradation of the extracellular matrix.

Protein family/group databases

MEROPSiM10.021.

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix metalloproteinase-19 (EC:3.4.24.-)
Short name:
MMP-19
Alternative name(s):
Matrix metalloproteinase RASI
Matrix metalloproteinase-18
Short name:
MMP-18
Gene namesi
Name:MMP19
Synonyms:MMP18, RASI
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:7165. MMP19.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: Reactome
  • proteinaceous extracellular matrix Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Cavitary optic disc anomalies (CODA)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn ocular disease characterized by a profound excavation of the optic nerve. Clinical phenotype is variable and includes congenitally excavated optic nerves as well as other features of optic pit, optic nerve coloboma, and morning glory disc anomaly. Patients with CODA have a strong predilection for retinal detachment and/or separation of the retinal layers (retinoschisis) that lead to profound central vision loss.
See also OMIM:611543

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi88E → P: Reduced autolysis rate. 1 Publication1
Mutagenesisi90P → V: Reduced autolysis rate. 1 Publication1

Organism-specific databases

DisGeNETi4327.
MIMi611543. phenotype.
OpenTargetsiENSG00000123342.
PharmGKBiPA30876.

Chemistry databases

ChEMBLiCHEMBL1938214.
DrugBankiDB00786. Marimastat.

Polymorphism and mutation databases

DMDMi12643345.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
PropeptideiPRO_000002882619 – 971 PublicationAdd BLAST79
ChainiPRO_000002882798 – 508Matrix metalloproteinase-19Add BLAST411

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi289 ↔ 472By similarity
Glycosylationi464N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Activated by autolytic cleavage after Lys-97.
Tyrosine phosphorylated by PKDCC/VLK.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

PaxDbiQ99542.
PeptideAtlasiQ99542.
PRIDEiQ99542.

PTM databases

iPTMnetiQ99542.
PhosphoSitePlusiQ99542.

Expressioni

Tissue specificityi

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 (PubMed:8920941).1 Publication

Gene expression databases

BgeeiENSG00000123342.
CleanExiHS_MMP19.
ExpressionAtlasiQ99542. baseline and differential.
GenevisibleiQ99542. HS.

Organism-specific databases

HPAiHPA012845.

Interactioni

Protein-protein interaction databases

IntActiQ99542. 1 interactor.
STRINGi9606.ENSP00000313437.

Chemistry databases

BindingDBiQ99542.

Structurei

3D structure databases

ProteinModelPortaliQ99542.
SMRiQ99542.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati286 – 333Hemopexin 1Add BLAST48
Repeati334 – 380Hemopexin 2Add BLAST47
Repeati381 – 425Hemopexin 3Add BLAST45
Repeati426 – 472Hemopexin 4Add BLAST47

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi83 – 90Cysteine switchBy similarity8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi265 – 271Poly-Glu7

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.
GeneTreeiENSGT00860000133713.
HOGENOMiHOG000217927.
HOVERGENiHBG052484.
InParanoidiQ99542.
KOiK07998.
OMAiRTDFSHY.
OrthoDBiEOG091G03DP.
PhylomeDBiQ99542.
TreeFamiTF315428.

Family and domain databases

CDDicd00094. HX. 1 hit.
cd04278. ZnMc_MMP. 1 hit.
Gene3Di1.10.101.10. 1 hit.
2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR033739. M10A_MMP.
IPR024079. MetalloPept_cat_dom.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PfamiPF00045. Hemopexin. 3 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.
PROSITEiPS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99542-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MNCQQLWLGF LLPMTVSGRV LGLAEVAPVD YLSQYGYLQK PLEGSNNFKP
60 70 80 90 100
EDITEALRAF QEASELPVSG QLDDATRARM RQPRCGLEDP FNQKTLKYLL
110 120 130 140 150
LGRWRKKHLT FRILNLPSTL PPHTARAALR QAFQDWSNVA PLTFQEVQAG
160 170 180 190 200
AADIRLSFHG RQSSYCSNTF DGPGRVLAHA DIPELGSVHF DEDEFWTEGT
210 220 230 240 250
YRGVNLRIIA AHEVGHALGL GHSRYSQALM APVYEGYRPH FKLHPDDVAG
260 270 280 290 300
IQALYGKKSP VIRDEEEEET ELPTVPPVPT EPSPMPDPCS SELDAMMLGP
310 320 330 340 350
RGKTYAFKGD YVWTVSDSGP GPLFRVSALW EGLPGNLDAA VYSPRTQWIH
360 370 380 390 400
FFKGDKVWRY INFKMSPGFP KKLNRVEPNL DAALYWPLNQ KVFLFKGSGY
410 420 430 440 450
WQWDELARTD FSSYPKPIKG LFTGVPNQPS AAMSWQDGRV YFFKGKVYWR
460 470 480 490 500
LNQQLRVEKG YPRNISHNWM HCRPRTIDTT PSGGNTTPSG TGITLDTTLS

ATETTFEY
Length:508
Mass (Da):57,357
Last modified:May 1, 1997 - v1
Checksum:iBA480549AA9A8972
GO
Isoform 2 (identifier: Q99542-3) [UniParc]FASTAAdd to basket
Also known as: RASI-9

The sequence of this isoform differs from the canonical sequence as follows:
     1-286: Missing.
     287-298: DPCSSELDAMML → MGVTWDFSMSNG

Show »
Length:222
Mass (Da):25,350
Checksum:i594DBE2F520DC0FE
GO
Isoform 3 (identifier: Q99542-4) [UniParc]FASTAAdd to basket
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.
Show »
Length:63
Mass (Da):6,931
Checksum:iC134E217099633E8
GO
Isoform 4 (identifier: Q99542-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     174-255: Missing.
     300-387: PRGKTYAFKG...PNLDAALYWP → EAPPLQAVGR...LASNTMDSLL
     388-508: Missing.

Note: No experimental confirmation available.
Show »
Length:305
Mass (Da):33,793
Checksum:i70E8A1C240863A8E
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti376V → S in CAA69913 (PubMed:8920941).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021036103R → C.1 PublicationCorresponds to variant rs17844794dbSNPEnsembl.1
Natural variantiVAR_054006245P → S.Corresponds to variant rs1056784dbSNPEnsembl.1
Natural variantiVAR_021037488P → T.1 PublicationCorresponds to variant rs17118042dbSNPEnsembl.1
Natural variantiVAR_021038491T → M.1 PublicationCorresponds to variant rs17844806dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0054571 – 286Missing in isoform 2. 1 PublicationAdd BLAST286
Alternative sequenceiVSP_04189358 – 63RAFQEA → SLRSAG in isoform 3. 1 Publication6
Alternative sequenceiVSP_04189464 – 508Missing in isoform 3. 1 PublicationAdd BLAST445
Alternative sequenceiVSP_054573174 – 255Missing in isoform 4. 1 PublicationAdd BLAST82
Alternative sequenceiVSP_005458287 – 298DPCSS…DAMML → MGVTWDFSMSNG in isoform 2. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_054574300 – 387PRGKT…ALYWP → EAPPLQAVGRRWGQPADPEA WTNGSDMGLQHEQWRAPWED LCFQGGLCVDCIRFRTGPLV PSVCPLGGAPRKPGCCCLLA SNTMDSLL in isoform 4. 1 PublicationAdd BLAST88
Alternative sequenceiVSP_054575388 – 508Missing in isoform 4. 1 PublicationAdd BLAST121

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AK303202 mRNA. Translation: BAG64292.1.
AY706993 Genomic DNA. Translation: AAT97983.1.
AC023055 Genomic DNA. No translation available.
BC050368 mRNA. Translation: AAH50368.1.
CCDSiCCDS61146.1. [Q99542-5]
CCDS8895.1. [Q99542-1]
PIRiJC5082.
RefSeqiNP_001259030.1. NM_001272101.1. [Q99542-5]
NP_002420.1. NM_002429.5. [Q99542-1]
UniGeneiHs.591033.

Genome annotation databases

EnsembliENST00000322569; ENSP00000313437; ENSG00000123342. [Q99542-1]
ENST00000409200; ENSP00000386625; ENSG00000123342. [Q99542-5]
ENST00000552872; ENSP00000446776; ENSG00000123342. [Q99542-4]
GeneIDi4327.
KEGGihsa:4327.
UCSCiuc001sib.5. human. [Q99542-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AK303202 mRNA. Translation: BAG64292.1.
AY706993 Genomic DNA. Translation: AAT97983.1.
AC023055 Genomic DNA. No translation available.
BC050368 mRNA. Translation: AAH50368.1.
CCDSiCCDS61146.1. [Q99542-5]
CCDS8895.1. [Q99542-1]
PIRiJC5082.
RefSeqiNP_001259030.1. NM_001272101.1. [Q99542-5]
NP_002420.1. NM_002429.5. [Q99542-1]
UniGeneiHs.591033.

3D structure databases

ProteinModelPortaliQ99542.
SMRiQ99542.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ99542. 1 interactor.
STRINGi9606.ENSP00000313437.

Chemistry databases

BindingDBiQ99542.
ChEMBLiCHEMBL1938214.
DrugBankiDB00786. Marimastat.

Protein family/group databases

MEROPSiM10.021.

PTM databases

iPTMnetiQ99542.
PhosphoSitePlusiQ99542.

Polymorphism and mutation databases

DMDMi12643345.

Proteomic databases

PaxDbiQ99542.
PeptideAtlasiQ99542.
PRIDEiQ99542.

Protocols and materials databases

DNASUi4327.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000322569; ENSP00000313437; ENSG00000123342. [Q99542-1]
ENST00000409200; ENSP00000386625; ENSG00000123342. [Q99542-5]
ENST00000552872; ENSP00000446776; ENSG00000123342. [Q99542-4]
GeneIDi4327.
KEGGihsa:4327.
UCSCiuc001sib.5. human. [Q99542-1]

Organism-specific databases

CTDi4327.
DisGeNETi4327.
GeneCardsiMMP19.
HGNCiHGNC:7165. MMP19.
HPAiHPA012845.
MIMi601807. gene.
611543. phenotype.
neXtProtiNX_Q99542.
OpenTargetsiENSG00000123342.
PharmGKBiPA30876.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
GeneTreeiENSGT00860000133713.
HOGENOMiHOG000217927.
HOVERGENiHBG052484.
InParanoidiQ99542.
KOiK07998.
OMAiRTDFSHY.
OrthoDBiEOG091G03DP.
PhylomeDBiQ99542.
TreeFamiTF315428.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000123342-MONOMER.
ReactomeiR-HSA-1442490. Collagen degradation.
R-HSA-1474228. Degradation of the extracellular matrix.

Miscellaneous databases

GeneWikiiMMP19.
GenomeRNAii4327.
PROiQ99542.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000123342.
CleanExiHS_MMP19.
ExpressionAtlasiQ99542. baseline and differential.
GenevisibleiQ99542. HS.

Family and domain databases

CDDicd00094. HX. 1 hit.
cd04278. ZnMc_MMP. 1 hit.
Gene3Di1.10.101.10. 1 hit.
2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR033739. M10A_MMP.
IPR024079. MetalloPept_cat_dom.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PfamiPF00045. Hemopexin. 3 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.
PROSITEiPS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMMP19_HUMAN
AccessioniPrimary (citable) accession number: Q99542
Secondary accession number(s): B4E030
, O15278, O95606, Q99580
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: May 1, 1997
Last modified: November 30, 2016
This is version 172 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

Autoantigen anti-MMP19 are frequent in RA patients.1 Publication

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. 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.