Q6V1X1 · DPP8_HUMAN
- ProteinDipeptidyl peptidase 8
- GeneDPP8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids898 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2 (PubMed:11012666, PubMed:12534281, PubMed:12662155, PubMed:15039077, PubMed:15664838, PubMed:20536396, PubMed:29382749).
Acts as a key inhibitor of caspase-1-dependent monocyte and macrophage pyroptosis in resting cells by preventing activation of NLRP1 and CARD8 (PubMed:27820798, PubMed:29967349, PubMed:32796818).
Sequesters the cleaved C-terminal part of NLRP1 and CARD8, which respectively constitute the active part of the NLRP1 and CARD8 inflammasomes, in a ternary complex, thereby preventing their oligomerization and activation (PubMed:33731929, PubMed:33731932, PubMed:34019797).
The dipeptidyl peptidase activity is required to suppress NLRP1 and CARD8; however, neither NLRP1 nor CARD8 are bona fide substrates of DPP8, suggesting the existence of substrate(s) required for NLRP1 and CARD8 inhibition (By similarity).
Acts as a key inhibitor of caspase-1-dependent monocyte and macrophage pyroptosis in resting cells by preventing activation of NLRP1 and CARD8 (PubMed:27820798, PubMed:29967349, PubMed:32796818).
Sequesters the cleaved C-terminal part of NLRP1 and CARD8, which respectively constitute the active part of the NLRP1 and CARD8 inflammasomes, in a ternary complex, thereby preventing their oligomerization and activation (PubMed:33731929, PubMed:33731932, PubMed:34019797).
The dipeptidyl peptidase activity is required to suppress NLRP1 and CARD8; however, neither NLRP1 nor CARD8 are bona fide substrates of DPP8, suggesting the existence of substrate(s) required for NLRP1 and CARD8 inhibition (By similarity).
Catalytic activity
Activity regulation
Inhibited by zinc. Inhibited by the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfluorophosphate. Specifically inhibited by isoindoline derivatives (PubMed:11012666, PubMed:12662155, PubMed:15664838).
Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective inhibitor, which triggers pyroptosis in monocytes and macrophages (PubMed:27820798, PubMed:29967349, PubMed:32796818).
Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective inhibitor, which triggers pyroptosis in monocytes and macrophages (PubMed:27820798, PubMed:29967349, PubMed:32796818).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
208 μM | Ala-Pro-AMC | |||||
130 μM | Ala-Pro-AFC | |||||
120 μM | H-Ala-Pro-pNa | |||||
1420 μM | H-Ala-Ala-pNa | |||||
310 μM | H-Arg-Pro-pNa | |||||
2050 μM | H-Asp-Pro-pNa | |||||
480 μM | H-Gly-Pro-pNa |
pH Dependence
Optimum pH is 7.4-8.5. Little activity below pH 6.5.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 755 | Charge relay system | ||||
Sequence: S | ||||||
Active site | 833 | Charge relay system | ||||
Sequence: D | ||||||
Active site | 865 | Charge relay system | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Molecular Function | aminopeptidase activity | |
Molecular Function | dipeptidyl-peptidase activity | |
Molecular Function | serine-type peptidase activity | |
Biological Process | apoptotic process | |
Biological Process | immune response | |
Biological Process | negative regulation of programmed cell death | |
Biological Process | proteolysis |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameDipeptidyl peptidase 8
- EC number
- Short namesDP8
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ6V1X1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 275 | 13-fold reduction in affinity for Ala-Pro-AFC; no effect on subcellular location. | ||||
Sequence: E → K | ||||||
Mutagenesis | 451 | Reduced dimerization and reduced enzyme activity. | ||||
Sequence: D → F | ||||||
Mutagenesis | 755 | Abolishes activity; no effect on subcellular location. | ||||
Sequence: S → A | ||||||
Mutagenesis | 788 | Strongly reduced enzyme activity. | ||||
Sequence: D → A, S, or V | ||||||
Mutagenesis | 788 | Loss of enzyme activity. Loss of dimerization. | ||||
Sequence: D → E | ||||||
Mutagenesis | 833 | Abolishes activity; no effect on subcellular location. | ||||
Sequence: D → A | ||||||
Mutagenesis | 865 | Abolishes activity; no effect on subcellular location. | ||||
Sequence: H → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 911 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000122413 | 1-898 | UniProt | Dipeptidyl peptidase 8 | |||
Sequence: MWKRSEQMKIKSGKCNMAAAMETEQLGVEIFETADCEENIESQDRPKLEPFYVERYSWSQLKKLLADTRKYHGYMMAKAPHDFMFVKRNDPDGPHSDRIYYLAMSGENRENTLFYSEIPKTINRAAVLMLSWKPLLDLFQATLDYGMYSREEELLRERKRIGTVGIASYDYHQGSGTFLFQAGSGIYHVKDGGPQGFTQQPLRPNLVETSCPNIRMDPKLCPADPDWIAFIHSNDIWISNIVTREERRLTYVHNELANMEEDARSAGVATFVLQEEFDRYSGYWWCPKAETTPSGGKILRILYEENDESEVEIIHVTSPMLETRRADSFRYPKTGTANPKVTFKMSEIMIDAEGRIIDVIDKELIQPFEILFEGVEYIARAGWTPEGKYAWSILLDRSQTRLQIVLISPELFIPVEDDVMERQRLIESVPDSVTPLIIYEETTDIWINIHDIFHVFPQSHEEEIEFIFASECKTGFRHLYKITSILKESKYKRSSGGLPAPSDFKCPIKEEIAITSGEWEVLGRHGSNIQVDEVRRLVYFEGTKDSPLEHHLYVVSYVNPGEVTRLTDRGYSHSCCISQHCDFFISKYSNQKNPHCVSLYKLSSPEDDPTCKTKEFWATILDSAGPLPDYTPPEIFSFESTTGFTLYGMLYKPHDLQPGKKYPTVLFIYGGPQVQLVNNRFKGVKYFRLNTLASLGYVVVVIDNRGSCHRGLKFEGAFKYKMGQIEIDDQVEGLQYLASRYDFIDLDRVGIHGWSYGGYLSLMALMQRSDIFRVAIAGAPVTLWIFYDTGYTERYMGHPDQNEQGYYLGSVAMQAEKFPSEPNRLLLLHGFLDENVHFAHTSILLSFLVRAGKPYDLQIYPQERHSIRVPESGEHYELHLLHYLQENLGSRIAALKVI | |||||||
Modified residue (large scale data) | 495 | PRIDE | Phosphoserine | ||||
Sequence: S |
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitously expressed, with highest levels in testis, placenta, prostate, muscle and brain.
Induction
In activated T-cells.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer (PubMed:20536396, PubMed:29382749).
Forms a ternary complex with NLRP1, composed of a DPP8 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus) (By similarity).
Forms a ternary complex with CARD8, composed of a DPP8 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of CARD8 (Caspase recruitment domain-containing protein 8, C-terminus) (By similarity).
In the ternary complex, only one subunit of the DPP8 homodimer is bound to NLRP1 or CARD8 (By similarity).
Forms a ternary complex with NLRP1, composed of a DPP8 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus) (By similarity).
Forms a ternary complex with CARD8, composed of a DPP8 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of CARD8 (Caspase recruitment domain-containing protein 8, C-terminus) (By similarity).
In the ternary complex, only one subunit of the DPP8 homodimer is bound to NLRP1 or CARD8 (By similarity).
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Sequence & Isoforms
- Sequence statusComplete
This entry describes 6 isoforms produced by Alternative splicing.
Q6V1X1-1
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.
- Name1
- Length898
- Mass (Da)103,358
- Last updated2004-07-05 v1
- Checksum60B0D036F026DE2A
Q6V1X1-2
- Name2
- Differences from canonical
- 723-773: Missing
Q6V1X1-3
- Name3
- Differences from canonical
- 1-16: Missing
Q6V1X1-4
- Name4
Q6V1X1-5
- Name5
- Differences from canonical
- 674-722: Missing
Q6V1X1-6
- Name6
- Differences from canonical
- 358-530: Missing
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_013860 | 1-16 | in isoform 3 and isoform 4 | |||
Sequence: Missing | ||||||
Sequence conflict | 233 | in Ref. 5; BC040203 | ||||
Sequence: S → G | ||||||
Alternative sequence | VSP_013861 | 358-530 | in isoform 6 | |||
Sequence: Missing | ||||||
Sequence conflict | 570 | in Ref. 4; BAB55395 | ||||
Sequence: G → S | ||||||
Sequence conflict | 673 | in Ref. 6; AAQ13650 | ||||
Sequence: Q → K | ||||||
Alternative sequence | VSP_013863 | 674-722 | in isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_013862 | 674-773 | in isoform 4 | |||
Sequence: Missing | ||||||
Sequence conflict | 686 | in Ref. 6; AAQ13650 | ||||
Sequence: Y → F | ||||||
Sequence conflict | 693-694 | in Ref. 6; AAQ13650 | ||||
Sequence: AS → PF | ||||||
Sequence conflict | 701 | in Ref. 6; AAQ13650 | ||||
Sequence: V → G | ||||||
Sequence conflict | 709 | in Ref. 6; AAQ13650 | ||||
Sequence: H → P | ||||||
Sequence conflict | 720 | in Ref. 6; AAQ13650 | ||||
Sequence: Y → F | ||||||
Alternative sequence | VSP_013864 | 723-773 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 799-803 | in Ref. 6; AAQ13623 | ||||
Sequence: PDQNE → LTRMN | ||||||
Sequence conflict | 820 | in Ref. 6; AAQ13623 | ||||
Sequence: S → F |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF221634 EMBL· GenBank· DDBJ | AAG29766.1 EMBL· GenBank· DDBJ | mRNA | ||
AF221635 EMBL· GenBank· DDBJ | AAG29767.1 EMBL· GenBank· DDBJ | mRNA | ||
AF221636 EMBL· GenBank· DDBJ | AAG29768.1 EMBL· GenBank· DDBJ | mRNA | ||
AF221637 EMBL· GenBank· DDBJ | AAG29769.1 EMBL· GenBank· DDBJ | mRNA | ||
AY172659 EMBL· GenBank· DDBJ | AAO17261.1 EMBL· GenBank· DDBJ | mRNA | ||
AY354202 EMBL· GenBank· DDBJ | AAQ63887.1 EMBL· GenBank· DDBJ | mRNA | ||
AK000290 EMBL· GenBank· DDBJ | BAA91059.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AK027826 EMBL· GenBank· DDBJ | BAB55395.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC030688 EMBL· GenBank· DDBJ | AAH30688.3 EMBL· GenBank· DDBJ | mRNA | ||
BC040203 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
AF176779 EMBL· GenBank· DDBJ | AAQ13657.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AF175225 EMBL· GenBank· DDBJ | AAQ13650.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AF173382 EMBL· GenBank· DDBJ | AAQ13623.1 EMBL· GenBank· DDBJ | mRNA | Frameshift |