Summary for peptidase M12.214: ADAM19 peptidase

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Literature Human EST Mouse EST Substrates Inhibitors

 

Names
MEROPS NameADAM19 peptidase
Other namesadamalysin-19, meltrin beta
Name and HistoryADAM19 is a membrane-bound sheddase first identified in the Golgi where it sheds the ectodomain of neuregulin-1 (NRG1) (Yokozeki et al., 2007).
Domain architecture
MEROPS Classification
Classification Clan MA >> Subclan MA(M) >> Family M12 >> Subfamily B >> M12.214
HolotypeADAM19 peptidase (Mus musculus), Uniprot accession O35674 (peptidase unit: 207-409), MERNUM MER0002459
History Identifier created: MEROPS 3.03 (10 September 1998)
Activity
Catalytic typeMetallo
NC-IUBMBNot yet included in IUBMB recommendations.
Proteolytic eventsCutDB database (10 cleavages)
Activity statushuman: active (Wei et al., 2001)
mouse: active (Shirakabe et al. (2001))
Special inhibitorBatimastat, which also inhibits matrix metallopeptidases and ADAM8, is inhibitory (Chesneau et al., 2003).
StructureADAM19 consists of a propeptide, a metallopeptidase, a disintegrin and a cysteine-rich domain. There is a C-terminal transmembrane region followed by a cytoplasmic tail, which means that the majority of the protein is lumenal. There are furin processing sites between the propeptide and the metallopeptidase domain, and specific furin inhibitors block activation (Kang et al., 2002). The human precursor is also autolytically processed within the cysteine-rich domain (Kang et al., 2004).
LocationADAM19 is found in the Golgi in neurons (Yokozeki et al., 2007), bone marrow and other organs that generate immune cells (Dehmel et al., 2007). The gene is expressed in the heart, tail-bud, cranial and dorsal root ganglia and to a lesser extent skeletal muscle cells during embryonic development (Kurisaki et al., 2002).
PhysiologyThe ADAM19 cytosolic tail has been shown to bind to the Tks5(I) SH3 domain (Kleino et al., 2015). ADAM19 sheds heparin-binding epidermal growth factor, tumor necrosis factor and the amyloid precursor protein, but the shed peptides do not form amyloid deposits. The ADAM19 gene is upregulated in cancerous cell lines and human brain tumors such as astrocytoma and glioblastoma (Qi et al., 2009). The gene is also expressed in the placenta and may have a role in trophoblast physiology by reducing cell invasion (Zhao et al., 2009).
RNA splicingAn alternatively spliced form lacking the prodomain, metallopeptidase and disintegrin domains in found in dorsal root ganglia (Kurisaki et al., 2002).
KnockoutMice deficient in ADAM19 endopeptidase show severe vascular defects (Zhou et al., 2004).
Other databases TREEFAMhttp://www.treefam.org/family/TF314733
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage patternglp/vpa/-/aScissile bondS/s/l/- (based on 13 cleavages)
weblogo
Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 3 0 0 0 0 0 2 1
Pro 3 3 0 1 0 0 0 0
Ala 1 2 3 5 2 0 2 1
Val 0 5 1 0 0 0 0 2
Leu 3 1 2 1 1 0 4 0
Ile 0 0 0 0 0 0 0 0
Met 0 0 0 0 0 0 1 0
Phe 0 0 0 0 1 0 1 0
Tyr 0 1 0 0 0 1 0 0
Trp 0 0 0 0 0 0 0 0
Ser 0 1 2 2 8 6 1 1
Thr 0 0 0 0 0 1 0 1
Cys 0 0 0 0 0 0 0 0
Asn 0 0 0 0 0 1 0 0
Gln 1 0 2 0 1 1 0 1
Asp 1 0 0 0 0 0 0 1
Glu 0 0 1 1 0 0 0 0
Lys 0 0 1 1 0 1 1 0
Arg 1 0 1 2 0 1 1 4
His 0 0 0 0 0 1 0 1
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
ADAM19 5q32-33 ENSG00000135074 8728 ADAM19 603640
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Adam19 11:A5-B1.1 ENSMUSG00000011256 11492 MGI:105377