Table 1.
| Clan SC | |||||||
|---|---|---|---|---|---|---|---|
| Family S9b (DPP4‐gene family) | S28 | ||||||
| DPP4 | FAP | DPL1 | DPL2 | DPP8 | DPP9 | DPP2 | |
| Synonyms |
DPIV, DPPIV, DAP IV, CD26, ADAbp, Gp108, Gp110, Hep105 |
Seprase, anti‐plasmin cleaving enzyme, APCE |
DP 6, DPP 6, DPPX‐S, DPPX‐L, DPPX |
DP 10, DPP 10, DPP Y |
DPP 8 | DPP 9 | DP II, DPP7, QPP |
| EC number | 3.4.14.5 | 3.4.21.B28 | – | – | – | – | 3.4.14.2 |
| Merops | S09.003 | S09.007 | S09.973 | S09.974 | S09.018 | S09.019 | S28.002 |
| Accession | M80536 | U09278 |
M96859 M96860 |
AY172659 | AF221634 | AF452102 | AF154502 |
| Gene location | 2q24.3 | 2q23 | 7q36.2–3 | 2q12.3–2q14.2 | 15q22 | 19p13.3 | 9q34.3 |
| Gene size (kb) | 81.8 | 72.8 | 659 | 535 | 71 | 48.7 | 2.85 |
| # Exons | 26 | 26 | 26 | 26 | 20 | 22 | 13 |
| Promoter | TATA‐less, GC rich | ? | ? | ? |
TATA‐less, GC rich |
? | ? |
| Regulation of expression |
Tissue‐specific HNFα/β Interferons α/β/γ RA, cytokines |
? | ? | ? | ? | ? | KLF2, TOB1 |
| # Amino acids | 766 | 760 | 803/859 | 796 | 882 | 863 | 492 |
| Mr (kDa) | 110 | 97 | 115/120 | 91 | 100 | 98 | 54.3 |
| Proform | – | – | – | – | – | – | yes (SP) |
| Transmembrane | ✔ | ✔ | ✔ | ✔ | – | – | – |
| Cysteines | 12 | 13 | 11 | 9 | 12 | 17 | 8 |
| # Glycosylation | 9 (2–9)* | 5 | 7 | 10 | ‐ | 2 | 6 |
| Glycosylation | N/O | N | N | N | ‐ | N | N |
| Catalytic triad | ✔ | ✔ | – | – | ✔ | ✔ | ✔ |
| Intron at catalytic S | ✔ | ✔ | – | – | – | – | ✔ |
| Activity | DPP4 | DPP4 + gelatinase | Unknown | Unknown | DPP4 | DPP4 | DPP4 (acidic pH) |
| Quaternary structure | dimer/tetramer | Dimer | Dimer | Dimer | Dimer | Dimer | Dimer |
| Activity needs dimer | ✔ | ✔ | – | – | – | – | ✔ |
| Crystal structure | ✔ | ✔ | ✔ | ✔ | – | – | ✔ |
| Subcellular location | Membrane type II/soluble | Membrane type II/soluble | Membrane type II | Membrane type II | Cytosolic |
Cytosolic/ Nuclear |
Secretory vesicles Lysosomes |
| Binding partners |
ADA, CD45, Cav‐1 Collagen, Glypican‐3, PgR, CARMA‐1, HIV‐TAT, CXCR‐4, M6P/IGFII, FAP |
α3β1 Integrins α5β1 Integrins Annexin 2 uPA‐R, DPP4 |
A‐type K(+) channel (Kv4.2) | A‐type K(+) channel (Kv4.2) | H‐Ras | H‐Ras | ADA |
| Distribution |
Ubiquitous Kidney > small intestine > lung |
Activated‐ Fibroblasts Activated‐ Stellate cells |
Brain | Brain, pancreas, adrenal gland |
Ubiquitous Reproductive Organs, brain |
Ubiquitous Heart, liver Skeletal, brain, muscle, testis |
Ubiquitous kidney, testis,brain |
| Knock‐out | ✔ | ✔ | ✔ | – | – | ✔ | ✔ |
| Transgenic | ✔ | – | – | – | – | – | – |
| Leucocytes |
⇑ act.# T cells, ⇑ act.# B cells ⇑ act.# NK cells ⇑ act.# Macrophages |
– | – | – |
⇑ Peripheral Leucocytes Lymphocytes ≈ Monocytes |
⇑ Peripheral leucocytes Lymphocytes ≈ Monocytes |
⇑ Macrophages Resting Lymphocytes |
| Known physiological functions |
Cell adhesion, Immune response, tumour progression, Psychoneuro‐endocrine function, metabolism |
Cell growth regulation, Tumour progression, wound‐healing Fibrogenesis |
Embryonic development, Signal transduction, regulation of synaptic plasticity, K+ channel |
Signal transduction, Regulation of synapticplasticity, K+ channel |
T‐cellproliferation? Signal Transduction Cell‐survival Cell‐proliferation |
Antigen presenting Signal transduction Cell‐survival Cell‐proliferation |
Neuroprotection? Maintaining lymphocyte quiescence |
| Pathological role |
Diabetes Cancer MS, AIDS Anxiety |
Cancer, Liver Cirrhosis Arthritis Pulmonary fibrosis |
Neurodegeneration Progressive spinal muscular atrophy |
Asthma Amyotrophic lateral sclerosis (ALS) |
Breast ‐, ovary cancer | Prostate cancer |
Apoptosis of leucocytes Neuroprotection diabetes |
| References | 6, 7, 8, 13, 59, 140, 141 | 6, 7, 13, 21, 22, 23, 28, 94 | 4, 6, 7, 44, 63, 64, 65, 66, 133 | 5, 6, 7, 61, 62, 69 | 2, 6, 7, 13, 31, 33, 34, 35, 94 | 6, 7, 13, 35, 36, 38, 39, 40, 41 | 6, 7, 75, 76, 77, 78, 80, 81, 82, 83, 84, 85, 86, 117 |
(2–9)* = Number of glycosylation sites being occupied in the crystal structures; # = activated. ADA = adenosine deaminase.