Q99542 (MMP19_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	508 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Secreted › extracellular space › extracellular 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-like domains.
Sequence caution	The sequence AAC99995.1 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.

Ontologies

Keywords
Biological process	Angiogenesis Collagen degradation Differentiation
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Developmental protein Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW collagen catabolic process Inferred from electronic annotation. Source: UniProtKB-KW luteolysis Inferred from electronic annotation. Source: Compara ovarian follicle development Inferred from electronic annotation. Source: Compara ovulation from ovarian follicle Inferred from electronic annotation. Source: Compara proteolysis Non-traceable author statement Ref.2. Source: UniProtKB response to cAMP Inferred from electronic annotation. Source: Compara response to hormone stimulus Inferred from electronic annotation. Source: Compara
Cellular_component	proteinaceous extracellular matrix Non-traceable author statement Ref.8. Source: UniProtKB
Molecular_function	calcium 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Propeptide	19 – 97	79			PRO_0000028826
	Chain	98 – 508	411	Matrix metalloproteinase-19		PRO_0000028827
Regions
	Domain	293 – 335	43	Hemopexin-like 1
	Domain	337 – 378	42	Hemopexin-like 2
	Domain	380 – 427	48	Hemopexin-like 3
	Domain	429 – 472	44	Hemopexin-like 4
	Motif	83 – 90	8	Cysteine switch By similarity
	Compositional bias	265 – 271	7	Poly-Glu
Sites
	Active site	213	1	By similarity
	Metal binding	85	1	Zinc; in inhibited form By similarity
	Metal binding	212	1	Zinc; catalytic By similarity
	Metal binding	216	1	Zinc; catalytic By similarity
	Metal binding	222	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	464	1	N-linked (GlcNAc...) Potential
	Disulfide bond	289 ↔ 472		By similarity
Natural variations
	Alternative sequence	1 – 286	286	Missing in isoform 2.		VSP_005457
	Alternative sequence	58 – 63	6	RAFQEA → SLRSAG in isoform 3.		VSP_041893
	Alternative sequence	64 – 508	445	Missing in isoform 3.		VSP_041894
	Alternative sequence	287 – 298	12	DPCSS…DAMML → MGVTWDFSMSNG in isoform 2.		VSP_005458
	Natural variant	103	1	R → C. Ref.6 Corresponds to variant rs17844794 [ dbSNP | Ensembl ].		VAR_021036
	Natural variant	245	1	P → S. Corresponds to variant rs1056784 [ dbSNP | Ensembl ].		VAR_054006
	Natural variant	488	1	P → T. Ref.6 Corresponds to variant rs17118042 [ dbSNP | Ensembl ].		VAR_021037
	Natural variant	491	1	T → M. Ref.6 Corresponds to variant rs17844806 [ dbSNP | Ensembl ].		VAR_021038
Experimental info
	Mutagenesis	88	1	E → P: Reduced autolysis rate.
	Mutagenesis	90	1	P → V: Reduced autolysis rate.
	Sequence conflict	376	1	V → S in CAA69913. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (RASI-1) (RASI-11) [UniParc]. Last modified May 1, 1997. Version 1. Checksum: BA480549AA9A8972	FASTA	508	57,357
	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
	Isoform 2 (RASI-9) [UniParc]. Checksum: 594DBE2F520DC0FE	FASTA	222	25,350
	10 20 30 40 50 60 MGVTWDFSMS NGGPRGKTYA FKGDYVWTVS DSGPGPLFRV SALWEGLPGN LDAAVYSPRT 70 80 90 100 110 120 QWIHFFKGDK VWRYINFKMS PGFPKKLNRV EPNLDAALYW PLNQKVFLFK GSGYWQWDEL 130 140 150 160 170 180 ARTDFSSYPK PIKGLFTGVP NQPSAAMSWQ DGRVYFFKGK VYWRLNQQLR VEKGYPRNIS 190 200 210 220 HNWMHCRPRT IDTTPSGGNT TPSGTGITLD TTLSATETTF EY
	Isoform 3 (RASI-6) [UniParc]. Checksum: C134E217099633E8	FASTA	63	6,931
	10 20 30 40 50 60 MNCQQLWLGF LLPMTVSGRV LGLAEVAPVD YLSQYGYLQK PLEGSNNFKP EDITEALSLR SAG

References

	« Hide 'large scale' referencesShow '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

NIEHS-SNPs

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.
IPI	IPI00016067. IPI00218151. IPI00218152. IPI00791255.
PIR	JC5082.
RefSeq	NP_002420.1. NM_002429.5.
UniGene	Hs.591033.
3D structure databases
ProteinModelPortal	Q99542.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99542. 1 interaction.
STRING	9606.ENSP00000313437.
Protein family/group databases
MEROPS	M10.021.
PTM databases
PhosphoSite	Q99542.
Polymorphism databases
DMDM	12643345.
Proteomic databases
PaxDb	Q99542.
PRIDE	Q99542.
Protocols and materials databases
DNASU	4327.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000322569; ENSP00000313437; ENSG00000123342. ENST00000394182; ENSP00000377736; ENSG00000123342. ENST00000552872; ENSP00000446776; ENSG00000123342.
GeneID	4327.
KEGG	hsa:4327.
UCSC	uc001sia.3. human. uc001sib.3. human.
Organism-specific databases
CTD	4327.
GeneCards	GC12M056230.
HGNC	HGNC:7165. MMP19.
HPA	HPA012845.
MIM	601807. gene.
neXtProt	NX_Q99542.
PharmGKB	PA30876.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG295915.
HOGENOM	HOG000217927.
HOVERGEN	HBG052484.
InParanoid	Q99542.
KO	K07998.
OMA	GYPRDTA.
OrthoDB	EOG495ZRW.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization. REACT_150387. Gelatin degradation by MMP19.
Gene expression databases
ArrayExpress	Q99542.
Bgee	Q99542.
CleanEx	HS_MMP19.
Genevestigator	Q99542.
GermOnline	ENSG00000123342. Homo sapiens.
Family and domain databases
Gene3D	1.10.101.10. 1 hit. 2.110.10.10. 1 hit. 3.40.390.10. 1 hit.
InterPro	IPR000585. Hemopexin-like_dom. IPR018487. Hemopexin-like_repeat. IPR024079. MetalloPept_cat_dom. IPR001818. Pept_M10_metallopeptidase. IPR021190. Pept_M10A. IPR016293. Pept_M10A_Metazoans. IPR006026. Peptidase_Metallo. IPR002477. Peptidoglycan-bd-like. [Graphical view]
Pfam	PF00045. Hemopexin. 3 hits. PF00413. Peptidase_M10. 1 hit. PF01471. PG_binding_1. 1 hit. [Graphical view]
PIRSF	PIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTS	PR00138. MATRIXIN.
SMART	SM00120. HX. 4 hits. SM00235. ZnMc. 1 hit. [Graphical view]
SUPFAM	SSF50923. Hemopexin. 1 hit. SSF47090. PGBD_like. 1 hit.
PROSITE	PS00546. CYSTEINE_SWITCH. False negative. PS00024. HEMOPEXIN. False negative. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q99542.
ChEMBL	CHEMBL1938214.
GenomeRNAi	4327.
NextBio	17029.
SOURCE	Search...

Entry information

Entry name

MMP19_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 138 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.