Summary for peptidase S09.003: dipeptidyl-peptidase IV (eukaryote)

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

 

Names
MEROPS Namedipeptidyl-peptidase IV (eukaryote)
Other namesCD26, dipeptidyl aminopeptidase IV, glycoprotein GP110, Gly-Pro naphthylamidase, lymphocyte antigen CD26, plasminogen receptor, type 2, postproline dipeptidyl aminopeptidase IV, thymocyte-activating molecule (Mus musculus), Xaa-Pro-dipeptidyl-aminopeptidase, adenosine deaminase binding protein
Domain architecture
MEROPS Classification
Classification Clan SC >> Subclan (none) >> Family S9 >> Subfamily B >> S09.003
Holotypedipeptidyl-peptidase IV (eukaryote) (Homo sapiens), Uniprot accession P27487 (peptidase unit: 503-766), MERNUM MER0000401
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeSerine
PeplistIncluded in the Peplist with identifier PL00368
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.14 (Dipeptidyl-peptidase and tripeptidyl-peptidases) >> Peptidase 3.4.14.5
EnzymologyBRENDA database
Proteolytic eventsCutDB database (9 cleavages)
Activity statushuman: active (Misumi & Ikehara, 2004)
mouse: active (Reimer et al., 2002)
PhysiologyDipeptidyl-peptidase IV has numerous biological functions in eukaryotes, including involvement in T-cell activation, cell adhesion, digestion of proline containing peptides in the kidney and intestines, HIV infection and apoptosis, and regulation of tumorigenicity in certain melanoma cells (Pethiyagoda et al., 2001). Amongst the important activities is the destruction of the insulinotropic hormone, glucagon-like peptide 1 (GLP-1) (Holst & Deacon, 1998; Deacon & Holst, 2002).
KnockoutFischer 344/CRJ rats harbor a G633R substitution in the gene that leads to retention and degradation of the mutant protein in the endoplasmic reticulum (Tsuji et al., 1992). The strain has been used as a knockout model to study involvement of the enzyme in metabolism of polypeptide hormones (Pederson et al., 1996) and tumor metastasis (Cheng et al., 1999).
Pharmaceutical relevanceInhibition of DPPIV is a rational strategy to treat type II diabetes, in view of the sparing effect that inhibitors have on the glucagon-like peptide 1 (GLP-1) that is normally metabolised by this enzyme (Nagakura et al., 2001). Long-term inhibition was found to improve glucose tolerance in both normal and glucose-intolerant mice (Reimer et al., 2002).
Pathways KEGGProtein digestion and absorption
Other databases TREEFAMhttp://www.treefam.org/family/TF313309
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/g/PScissile bond-/-/-/- (based on 27 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 0 0 6 1 0 2 0 1
Pro 0 0 0 20 0 2 0 2
Ala 0 0 4 3 2 3 5 0
Val 0 0 3 0 3 1 1 1
Leu 0 0 0 0 4 1 1 0
Ile 0 0 0 0 0 0 1 0
Met 0 0 0 0 1 0 2 0
Phe 0 0 1 0 0 2 0 1
Tyr 0 0 3 0 3 0 0 0
Trp 0 0 0 0 0 0 0 0
Ser 0 0 1 0 1 5 1 1
Thr 0 0 1 0 0 1 2 2
Cys 0 0 0 1 0 0 0 0
Asn 0 0 0 0 0 1 0 2
Gln 0 0 1 0 0 0 1 1
Asp 0 0 0 1 2 0 0 2
Glu 0 0 0 0 2 0 1 3
Lys 0 0 1 0 1 0 2 1
Arg 0 0 2 0 0 1 2 2
His 0 0 1 0 0 0 0 0
Specificity from combinatorial peptides
 
Organism comment P4 P3 P2 P1 P1' P2' P3' P4' optimal substrate fluorophore or acceptor-donor pair Reference
Homo sapiens recombinant xxx xxx n/broad P - - - - n P AMC Leiting et al., 2003
Homo sapiens recombinant xxx xxx P/broad P - - - - PP AMC Edosada et al., 2006
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
DPP4 2q23-qter ENSG00000169536 1803 DPP4 102720
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Dpp4 2:C2-D ENSMUSG00000035000 13482 MGI:94919