Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

DPP4 (P27487) - Overview - Molecular Target Synopsis

Protein


DPP4, Dipeptidyl peptidase 4
Enzyme Classification 3.4.14.5
UniProt P27487

Also Known as DPP4_HUMAN, DPP4, ADCP2, CD26

Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline. Monomer. Homodimer (PubMed:12832764, PubMed:15448155, PubMed:17287217, PubMed:12646248, PubMed:12483204, PubMed:12906826). Heterodimer with Seprase (FAP) (PubMed:16651416). Requires homodimerization for optimal dipeptidyl peptidase activity and T-cell costimulation. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB (PubMed:17287217). Associates with collagen (PubMed:8526932). Interacts with PTPRC; the interaction is enhanced in a interleukin-12-dependent manner in activated lymphocytes (PubMed:12676959). Interacts (via extracellular domain) with ADA; does not inhibit its dipeptidyl peptidase activity (PubMed:15016824, PubMed:10951221, PubMed:14691230, PubMed:7907293, PubMed:8101391). Interacts with CAV1 (via the N-terminus); the interaction is direct (PubMed:17287217). Interacts (via cytoplasmic tail) with CARD11 (via PDZ domain); its homodimerization is necessary for interaction with CARD11 (PubMed:17287217). Interacts with IGF2R; the interaction is direct (PubMed:10900005). Interacts with GPC3 (PubMed:17549790). Interacts with human coronavirus-EMC spike protein and acts as a receptor for this virus (PubMed:23486063).

5ZID
CRYSTAL STRUCTURE OF HUMAN DPP-IV IN COMPLEX WITH HL2
RCSB/PDB
Inspect Structure
See all 3D Structures for DPP4

Isoforms / Transcripts (Protein Coding)


Drugs


DPP4 is targeted by Approved Drugs Vildagliptin, Sitagliptin, Linagliptin. (see details)
Vildagliptin
Sitagliptin
Linagliptin

Sub-cellular localization


UniProt: DPP4 is active in the following subcellular-locations: apical cell membrane, cell junction, cell membrane, cell projection, invadopodium membrane, lamellipodium membrane, membrane raft, secreted.
GO terms: DPP4 is active in the following subcellular-locations: apical plasma membrane, cell surface, endocytic vesicle, extracellular exosome, extracellular region, focal adhesion, integral component of membrane, intercellular canaliculus, invadopodium membrane, lamellipodium, lamellipodium membrane, lysosomal membrane, membrane, membrane raft, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project DPP4 has gain in 0 cell-lines, loss in 1 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: IGROV1, KM12, PC_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OVMANA, Hs 675.T, HCC89

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, AG445, hMSC-AT

(see details)

3D Structures


For DPP4 there are:
104 structures (253 chains) solved
104 are solved in complex with at least one small molecule ligand
3 are solved with an approved drug

DPP4 is solved in complex with the approved drug(s):

715/SITAGLIPTIN (1X70_A, 1X70_B),
356/LINAGLIPTIN (2RGU_A, 2RGU_B),
T22/ALOGLIPTIN (3G0B_A, 3G0B_B, 3G0B_C, 3G0B_D).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


DPP4 has been screened with 5229 compounds (7180 bioactivities), 3277 compounds have bioactivities that show binding affinity of <= 500nM (4172 bioactivities). (see details)