TREM1

Triggering receptor expressed on myeloid cells 1 is a protein that in humans is encoded by the TREM1 gene.[5][6][7]

TREM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1Q8M, 1SMO
Identifiers
Aliases	TREM1, CD354, TREM-1, triggering receptor expressed on myeloid cells 1
External IDs	OMIM: 605085 MGI: 1930005 HomoloGene: 10243 GeneCards: TREM1
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p21.1 Start 41,267,926 bp[1] End 41,286,682 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 C Start 48,232,768 bp[2] End 48,246,924 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • scaffold protein binding • signaling receptor activity Cellular component • integral component of membrane • membrane • cell membrane • extracellular region • intracellular Biological process • GO:0007243 intracellular signal transduction • humoral immune response • regulation of immune response • innate immune system • leukocyte migration • acute inflammatory response Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	54210	58217
Ensembl	ENSG00000124731	ENSMUSG00000042265
UniProt	Q9NP99	Q9JKE2
RefSeq (mRNA)	NM_001242589 NM_001242590 NM_018643	NM_021406 NM_001347399
RefSeq (protein)	NP_001229518 NP_001229519 NP_061113	NP_001334328 NP_067381
Location (UCSC)	Chr 6: 41.27 – 41.29 Mb	Chr 17: 48.23 – 48.25 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Monocyte/macrophage- and neutrophil-mediated inflammatory responses can be stimulated through a variety of receptors, including G protein-linked 7-transmembrane receptors (e.g., FPR1), Fc receptors (see MIM 146790), CD14 and Toll-like receptors (e.g., TLR4), and cytokine receptors (e.g., IFNGR1; MIM 107470). Engagement of these receptors can also prime myeloid cells to respond to other stimuli. Myeloid cells express receptors belonging to the Ig superfamily, such as TREM1, or to the C-type lectin superfamily. Depending on their transmembrane and cytoplasmic sequence structure, these receptors have either activating (e.g., KIR2DS1; MIM 604952) or inhibitory functions (e.g., KIR2DL1).[7] In granulocyte cells, TREM1 is activated by C/EBPε independently from inflammatory response.[8]

Model organisms

Model organisms have been used in the study of TREM1 function. A conditional knockout mouse line called Trem1^{tm1(KOMP)Vlcg} was generated at the Wellcome Trust Sanger Institute.[9] Male and female animals underwent a standardized phenotypic screen[10] to determine the effects of deletion.[11][12][13][14] Additional screens performed: - In-depth immunological phenotyping[15]

Trem1 knockout mouse phenotype

Characteristic	Phenotype
All data available at.[10][15]
Insulin	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Epidermal Immune Composition	Normal
Influenza Challenge	Normal

References

1. GRCh38: Ensembl release 89: ENSG00000124731 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000042265 - 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. Gingras MC, Lapillonne H, Margolin JF (March 2002). "TREM-1, MDL-1, and DAP12 expression is associated with a mature stage of myeloid development". Molecular Immunology. 38 (11): 817–24. doi:10.1016/S0161-5890(02)00004-4. PMID 11922939.
6. Bouchon A, Dietrich J, Colonna M (May 2000). "Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes". Journal of Immunology. 164 (10): 4991–5. doi:10.4049/jimmunol.164.10.4991. PMID 10799849.
7. "Entrez Gene: TREM1 triggering receptor expressed on myeloid cells 1".
8. Suh HC, Benoukraf T, Shyamsunder P, Yin T, Cao Q, Said J, Lee S, Lim R, Yang H, Salotti J, Johnson PF, Madan V, Koeffler HP (April 2017). "LPS independent activation of the pro-inflammatory receptor Trem1 by C/EBPε in granulocytes". Scientific Reports. 7: 46440. doi:10.1038/srep46440. PMC 5404328. PMID 28440307.
9. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
10. "International Mouse Phenotyping Consortium".
11. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
12. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
13. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
14. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, et al. (July 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
15. "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Bouchon A, Facchetti F, Weigand MA, Colonna M (April 2001). "TREM-1 amplifies inflammation and is a crucial mediator of septic shock". Nature. 410 (6832): 1103–7. doi:10.1038/35074114. PMID 11323674.
• Allcock RJ, Barrow AD, Forbes S, Beck S, Trowsdale J (February 2003). "The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44". European Journal of Immunology. 33 (2): 567–77. doi:10.1002/immu.200310033. PMID 12645956.
• Bleharski JR, Kiessler V, Buonsanti C, Sieling PA, Stenger S, Colonna M, Modlin RL (April 2003). "A role for triggering receptor expressed on myeloid cells-1 in host defense during the early-induced and adaptive phases of the immune response". Journal of Immunology. 170 (7): 3812–8. doi:10.4049/jimmunol.170.7.3812. PMID 12646648.
• Colonna M, Facchetti F (June 2003). "TREM-1 (triggering receptor expressed on myeloid cells): a new player in acute inflammatory responses". The Journal of Infectious Diseases. 187 Suppl 2: S397-401. doi:10.1086/374754. PMID 12792857.
• Radaev S, Kattah M, Rostro B, Colonna M, Sun PD (December 2003). "Crystal structure of the human myeloid cell activating receptor TREM-1". Structure. 11 (12): 1527–35. doi:10.1016/j.str.2003.11.001. PMID 14656437.
• Radsak MP, Salih HR, Rammensee HG, Schild H (April 2004). "Triggering receptor expressed on myeloid cells-1 in neutrophil inflammatory responses: differential regulation of activation and survival". Journal of Immunology. 172 (8): 4956–63. doi:10.4049/jimmunol.172.8.4956. PMID 15067076.
• Wang DY, Qin RY, Liu ZR, Gupta MK, Chang Q (September 2004). "Expression of TREM-1 mRNA in acute pancreatitis". World Journal of Gastroenterology. 10 (18): 2744–6. doi:10.3748/wjg.v10.i18.2744. PMC 4572206. PMID 15309732.
• Kelker MS, Foss TR, Peti W, Teyton L, Kelly JW, Wüthrich K, Wilson IA (September 2004). "Crystal structure of human triggering receptor expressed on myeloid cells 1 (TREM-1) at 1.47 A". Journal of Molecular Biology. 342 (4): 1237–48. doi:10.1016/j.jmb.2004.07.089. PMID 15351648.
• Knapp S, Gibot S, de Vos A, Versteeg HH, Colonna M, van der Poll T (December 2004). "Cutting edge: expression patterns of surface and soluble triggering receptor expressed on myeloid cells-1 in human endotoxemia". Journal of Immunology. 173 (12): 7131–4. doi:10.4049/jimmunol.173.12.7131. PMID 15585833.
• González-Roldán N, Ferat-Osorio E, Aduna-Vicente R, Wong-Baeza I, Esquivel-Callejas N, Astudillo-de la Vega H, Sánchez-Fernández P, Arriaga-Pizano L, Villasís-Keever MA, López-Macías C, Isibasi A (December 2005). "Expression of triggering receptor on myeloid cell 1 and histocompatibility complex molecules in sepsis and major abdominal surgery". World Journal of Gastroenterology. 11 (47): 7473–9. doi:10.3748/wjg.v11.i47.7473. PMC 4723392. PMID 16437719.
• Tzivras M, Koussoulas V, Giamarellos-Bourboulis EJ, Tzivras D, Tsaganos T, Koutoukas P, Giamarellou H, Archimandritis A (June 2006). "Role of soluble triggering receptor expressed on myeloid cells in inflammatory bowel disease". World Journal of Gastroenterology. 12 (21): 3416–9. doi:10.3748/wjg.v12.i21.3416. PMC 4087875. PMID 16733861.
• Plachouras D, Routsi C, Giamarellos-Bourboulis EJ, Spyridaki E, Andrianakis I, Metzelopoulos S, Tsaganos T, Floros I, Douzinas EE, Armaganidis A, Roussos C, Giamarellou H (2006). "Monocytes as a site of production of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the septic host". Scandinavian Journal of Infectious Diseases. 38 (10): 909–15. doi:10.1080/00365540600786523. PMID 17008237.
• Murakami Y, Kohsaka H, Kitasato H, Akahoshi T (January 2007). "Lipopolysaccharide-induced up-regulation of triggering receptor expressed on myeloid cells-1 expression on macrophages is regulated by endogenous prostaglandin E2". Journal of Immunology. 178 (2): 1144–50. doi:10.4049/jimmunol.178.2.1144. PMID 17202378.