DPP9

Last updated
DPP9
Identifiers
Aliases DPP9 , DP9, DPLP9, DPRP-2, DPRP2, dipeptidyl peptidase 9, DPP IX
External IDs OMIM: 608258 MGI: 2443967 HomoloGene: 16385 GeneCards: DPP9
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_139159
NM_001365987

NM_172624
NM_001360284

RefSeq (protein)

NP_631898
NP_001352916

NP_766212
NP_001347213

Location (UCSC) Chr 19: 4.68 – 4.72 Mb Chr 17: 56.49 – 56.53 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Dipeptidyl peptidase 9 is an enzyme that in humans is encoded by the DPP9 gene. [5]

Contents

This gene encodes a protein that is a member of the S9B family in clan SC of the serine proteases. The protein has been shown to have post-proline dipeptidyl aminopeptidase activity, cleaving Xaa-Pro dipeptides from the N-termini of proteins. Although the activity of this protein is similar to that of dipeptidyl peptidase 4 (DPP4), it does not appear to be membrane bound.

In general, dipeptidyl peptidases appear to be involved in the regulation of the activity of their substrates and have been linked to a variety of diseases including type 2 diabetes, obesity and cancer. Several transcript variants of this gene have been described but not fully characterized. [5] More specifically, DPP9 interacts with the NLRP1 protein and affects the level of activation of the NLRP1 inflammasome. This function involves binding to a complex of full-length NLRP1 and a proinflammatory fragment of NLRP1 after activation by autocleavage. [6] [7] A similar mechanism allows DPP9 to regulate the CARD8 inflammasome. [8]

This gene has also been linked to severe COVID-19.

Medical genetics

Mutations in NLRP1 that block DPP9 interaction lead to a rare Mendelian condition called Autoinflammation with Arthritis and Dyskeratosis [9] [10] A homozygous recessive syndrome dubbed Hatipoğlu syndrome is attributed to mutations in DPP9 with a phenotype of failure to thrive, skin manifestations, pancytopenia, and susceptibility to infections. [11] Genetic analysis of knockout alleles of DPP9 in mice and zebrafish showed a severe phenotype that could be rescued by mutation of NLPR1 in the same report.

Related Research Articles

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<span class="mw-page-title-main">HNF1A</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">NLRP1</span> Human protein-coding gene

NLRP1 encodes NACHT, LRR, FIIND, CARD domain and PYD domains-containing protein 1 in humans. NLRP1 was the first protein shown to form an inflammasome. NLRP1 is expressed by a variety of cell types, which are predominantly epithelial or hematopoietic. The expression is also seen within glandular epithelial structures including the lining of the small intestine, stomach, airway epithelia and in hairless or glabrous skin. NLRP1 polymorphisms are associated with skin extra-intestinal manifestations in CD. Its highest expression was detected in human skin, in psoriasis and in vitiligo. Polymorphisms of NLRP1 were found in lupus erythematosus and diabetes type 1. Variants of mouse NLRP1 were found to be activated upon N-terminal cleavage by the protease in anthrax lethal factor.

<span class="mw-page-title-main">DPP6</span> Protein-coding gene in the species Homo sapiens

Dipeptidyl aminopeptidase-like protein 6 is a protein that in humans is encoded by the DPP6 gene.

<span class="mw-page-title-main">NLRC4</span> Protein-coding gene in the species Homo sapiens

NLR family CARD domain-containing protein 4 is a protein that in humans is encoded by the NLRC4 gene.

<span class="mw-page-title-main">Attractin</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">DPP7</span> Protein-coding gene in the species Homo sapiens

Dipeptidyl-peptidase 2 is an enzyme that in humans is encoded by the DPP7 gene.

<span class="mw-page-title-main">DPP8</span> Protein-coding gene in humans

Dipeptidyl peptidase 8 is an enzyme that in humans is encoded by the DPP8 gene.

<span class="mw-page-title-main">DPP10</span> Protein-coding gene in the species Homo sapiens

Inactive dipeptidyl peptidase 10 is a protein that in humans is encoded by the DPP10 gene. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

<span class="mw-page-title-main">TSPAN8</span> Protein-coding gene in humans

Tetraspanin-8 is a protein that in humans is encoded by the TSPAN8 gene.

<span class="mw-page-title-main">DNPEP</span> Protein-coding gene in the species Homo sapiens

Aspartyl aminopeptidase is an enzyme that in humans is encoded by the DNPEP gene.

<span class="mw-page-title-main">USP53</span> Protein-coding gene in the species Homo sapiens

Inactive ubiquitin carboxyl-terminal hydrolase 53 is a protein that in humans is encoded by the USP53 gene.

NLRP (Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing), also abbreviated as NALP, is a type of NOD-like receptor. NOD-like receptors are a type of pattern recognition receptor that are found in the cytosol of the cell, recognizing signals of antigens in the cell. NLRP proteins are part of the innate immune system and detect conserved pathogen characteristics, or pathogen-associated molecular patterns, such as such as peptidoglycan, which is found on some bacterial cells. It is thought that NLRP proteins sense danger signals linked to microbial products, initiating the processes associated with the activation of the inflammasome, including K+ efflux and caspase 1 activation. NLRPs are also known to be associated with a number of diseases. Research suggests NLRP proteins may be involved in combating retroviruses in gametes. As of now, there are at least 14 different known NLRP genes in humans, which are named NLRP1 through NLRP14. The genes translate into proteins with differing lengths of leucine-rich repeat domains.

<span class="mw-page-title-main">SERPINA2</span> Protein-coding gene in the species Homo sapiens

Serpin peptidase inhibitor, clade A, member 2 is a protein that in humans is encoded by the SERPINA2 gene. Serine peptidase inhibitor, clade A member 2 belongs to the member of serine family of proteins which have a functional activity of inhibiting serine proteases.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000142002 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000001229 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Entrez Gene: DPP9 dipeptidyl-peptidase 9".
  6. Hollingsworth LR, Sharif H, Griswold AR, Fontana P, Mintseris J, Dagbay KB, et al. (April 2021). "DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation". Nature. 592 (7856): 778–783. Bibcode:2021Natur.592..778H. doi:10.1038/s41586-021-03350-4. PMC   8299537 . PMID   33731932.
  7. Huang M, Zhang X, Toh GA, Gong Q, Wang J, Han Z, et al. (April 2021). "Structural and biochemical mechanisms of NLRP1 inhibition by DPP9". Nature. 592 (7856): 773–777. Bibcode:2021Natur.592..773H. doi:10.1038/s41586-021-03320-w. PMC   8081665 . PMID   33731929.
  8. Sharif H, Hollingsworth LR, Griswold AR, Hsiao JC, Wang Q, Bachovchin DA, Wu H (July 2021). "Dipeptidyl peptidase 9 sets a threshold for CARD8 inflammasome formation by sequestering its active C-terminal fragment". Immunity. 54 (7): 1392–1404.e10. doi:10.1016/j.immuni.2021.04.024. PMC   8423358 . PMID   34019797.
  9. "Autoinflammation With Arthritis and Dyskeratosis; AIADK". Online Mendelian Inheritance in Man. 617388.
  10. Zhong FL, Robinson K, Teo DE, Tan KY, Lim C, Harapas CR, et al. (December 2018). "Human DPP9 represses NLRP1 inflammasome and protects against autoinflammatory diseases via both peptidase activity and FIIND domain binding". The Journal of Biological Chemistry. 293 (49): 18864–18878. doi: 10.1074/jbc.RA118.004350 . PMC   6295727 . PMID   30291141.
  11. Harapas CR, Robinson KS, Lay K, Wong J, Moreno Traspas R, Nabavizadeh N, Rass-Rothschild A, Boisson B, Drutman SB, Laohamonthonkul P, Bonner D, Xiong JR, Gorrell MD, Davidson S, Yu C, Fleming MD, Gudera J, Stein J, Ben-Harosh M, Groopman E, Shimamura A, Tamary H, Kayserili H, Hatipoğlu N, Casanova J, Bernstein JA, Zhong FL, Masters SL, Reversade B (September 2022). "DPP9 deficiency: An inflammasomopathy that can be rescued by lowering NLRP1/IL-1 signaling". Science Immunology. 7 (75): eabi4611. doi:10.1126/sciimmunol.abi4611. hdl: 10754/681562 . PMC   9844213 . PMID   36112693.

Further reading