Immunoglobulin like domain containing proteins

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Immunoglobulin like domain containing proteins

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Targets

3331

Targets of relevance to immunopharmacology are highlighted in blue

RAGE (advanced glycosylation end-product specific receptor) Show summary »« Hide summary More detailed page go icon to follow link

Target Id

2843

Nomenclature

advanced glycosylation end-product specific receptor

Common abbreviation

RAGE

Previous and unofficial names

advanced glycosylation end product-specific receptor

Genes

AGER (Hs), Ager (Mm), Ager (Rn)

Ensembl ID

ENSG00000204305 (Hs), ENSMUSG00000015452 (Mm), ENSRNOG00000000439 (Rn)

UniProtKB AC

Q15109 (Hs), Q62151 (Mm), Q63495 (Rn)

Antagonists

azeliragon pIC₅₀ ~6.0 [10,15]

Comment

RAGE is a single chain, membrane bound immunoglobulin type protein [13,17,22] which acts as a pattern recognition receptor for ligands containing a common glycation motif.

FcαRI (Fc fragment of IgA receptor / CD89) Show summary »« Hide summary More detailed page go icon to follow link

Target Id	2991
Nomenclature	Fc fragment of IgA receptor
Systematic nomenclature	CD89
Common abbreviation	FcαRI
Genes	FCAR (Hs), Fcar (Rn)
Ensembl ID	ENSG00000186431 (Hs), ENSRNOG00000027855 (Rn)
UniProtKB AC	P24071 (Hs)

Fc fragment of IgG receptor IIa Show summary »« Hide summary

Target Id	3190
Nomenclature	Fc fragment of IgG receptor IIa
Previous and unofficial names	Fc gamma receptor IIa \| FcγRIIA \| Fcgr3 \| Fcgr3a \| Immunoglobulin G Fc receptor II \| CD32a
Genes	FCGR2A (Hs), Fcgr3 (Mm), Fcgr2a (Rn)
Ensembl ID	ENSG00000143226 (Hs), ENSMUSG00000059498 (Mm), ENSRNOG00000046663 (Rn), ENSRNOG00000049422 (Rn)
UniProtKB AC	P12318 (Hs), P27645 (Rn)
Comment	Serum from patients with vaccine-induced immune thrombocytopenia and thrombosis (VITT; a serious but very rare adverse response to a chimpanzee adenovirus-based SARS-CoV-2 vaccine [6,19]) activates platelets via the FCGR2A (FcγRIIA) [20]. VITT can be managed with intravenous Ig infusion or plasma exchange, but these are expensive and limited resources. In vitro, pharmacological blockade of FcγRIIA-mediated platelet activation can be achieved by drugs that inhibit the function of COX enzymes, P2Y₁₂, or the Src, Syk and BTK kinases. This indicates that small molecules may have clinical potential as VITT therapies.

Fc fragment of IgG receptor IIIa / CD16A Show summary »« Hide summary More detailed page go icon to follow link

Target Id	3017
Nomenclature	Fc fragment of IgG receptor IIIa
Systematic nomenclature	CD16A
Previous and unofficial names	Fc receptor, IgG, low affinity IV \| Fc receptor \| Fc gamma receptor IIIa \| FCγRIIIa \| FcRIIIA \| low affinity immunoglobulin gamma Fc region receptor III-A
Genes	FCGR3A (Hs), Fcgr4 (Mm), Fcgr3a (Rn)
Ensembl ID	ENSG00000203747 (Hs), ENSMUSG00000059089 (Mm), ENSRNOG00000024382 (Rn)
UniProtKB AC	P08637 (Hs), A0A0B4J1G0 (Mm)

FcμRI (Fc fragment of IgM receptor) Show summary »« Hide summary More detailed page go icon to follow link

CD155 (PVR cell adhesion molecule) Show summary »« Hide summary More detailed page go icon to follow link

Target Id	3095
Nomenclature	PVR cell adhesion molecule
Common abbreviation	CD155
Previous and unofficial names	CD155 \| NECL5 \| nectin-like 5 \| poliovirus receptor \| Tage4
Genes	PVR (Hs)
Ensembl ID	ENSG00000073008 (Hs)
UniProtKB AC	P15151 (Hs)
Comment	PVR is the receptor that is expoited by the poliovirus to gain entry to host cells. It also contributes to a number of immunoregulatory functions through its interactions with activating and inhibitory immune cell receptors.

TIGIT Show summary »« Hide summary More detailed page go icon to follow link

Target Id	2941
Nomenclature	TIGIT
Previous and unofficial names	T-cell immunoreceptor with Ig and ITIM domains \| V-set and immunoglobulin domain containing 9 \| V-set and transmembrane domain containing 3 \| VSIG9 \| VSTM3 \| WUCAM [1]
Genes	TIGIT (Hs), Tigit (Mm), Tigit (Rn)
Ensembl ID	ENSG00000181847 (Hs), ENSMUSG00000071552 (Mm), ENSRNOG00000056574 (Rn)
UniProtKB AC	Q495A1 (Hs), P86176 (Mm)
Comment	TIGIT is an immune checkpoint modulator [8].

TREM2 (triggering receptor expressed on myeloid cells 2) Show summary »« Hide summary

Target Id

3331

Nomenclature

triggering receptor expressed on myeloid cells 2

Common abbreviation

TREM2

Previous and unofficial names

TREM-2 | triggering receptor expressed on myeloid cells 2a (Trem2a)

Genes

TREM2 (Hs), Trem2 (Mm), Trem2 (Rn)

Ensembl ID

ENSG00000095970 (Hs), ENSMUSG00000023992 (Mm), ENSRNOG00000013578 (Rn)

UniProtKB AC

Q9NZC2 (Hs), Q99NH8 (Mm)

Agonists

T2M-010 [4]

TREM2 agonist 4i [12]

TREM2 agonist C1 [25]

VG-3927 [25]

Comment

TREM2 is a membrane-bound receptor that contains an immunoglobulin V-set domain. It appears to function as a lipid-sensing receptor, with ligands including cyclophilin A [7], amyloid-β protein 42 [24,26], lipoprotein particles and apolipoproteins [24], and phospholipids [14]. Via interaction with TYROBP (TYROBP; DAP12) and spleen tyrosine kinase (SYK) phosphorylation, TREM2 regulates microglial survival, plasticity, migration and expression of inflammatory cytokines. Rare coding variants are associated with neurodegeneration in Alzheimer's disease [5,21,23]. The protein is an active target for the development of therapeutics for various neurodegenerative diseases [2-4,18,23,25]. VGL101 (iluzanebart), DNL919, and AL002 are agonistic TREM2-targeting monoclonal antibodies that are (or were) in clinical development for neurodegenerative diseases [9,11,16], although these are subject to limited brain permeability. This latter approach was proposed to activate TREM2-mediated microglial removal of amyloid β (Aβ) from the brain. In the phase 2 AL002 study changes resembling amyloid-related imaging abnormalities (ARIA) similar to those observed with the approved anti-Aβ monoclonals (aducanumab and lecanemab for example) were detected [11].

References

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1. Boles KS, Vermi W, Facchetti F, Fuchs A, Wilson TJ, Diacovo TG, Cella M, Colonna M. (2009) A novel molecular interaction for the adhesion of follicular CD4 T cells to follicular DC. Eur J Immunol, 39 (3): 695-703. [PMID:19197944]

2. Cho S, Gaamouch FE, Upadhyay S, Nada H, Kuncewicz K, Gabr MT. (2025) As48, a First-in-Class Dual-Function TREM2 Modulator: Receptor Activation and Shedding Inhibition. bioRxiv,. [PMID:40909719]

3. Cho S, Kaur B, Lam K, Gaamouch FE, Kuncewicz K, Doering NP, Wolber G, Gabr MT. (2025) Structure-Based Virtual Screening Identifies TREM2-Targeted Small Molecules that Enhance Microglial Phagocytosis. bioRxiv,. [PMID:40909477]

4. Cho S, Szalai TV, El Gaamouch F, Bajusz D, Keserű GM, Gabr M. (2025) AI-Assisted Discovery and Optimization of Small Molecule TREM2 Agonists with Functional Microglial Activity. bioRxiv,. [PMID:41000669]

5. Curtis D, Joseph S, Alzheimer’s Disease Neuroimaging Initiative. (2025) Analysis of whole genome sequence data shows association of Alzheimer's disease with rare coding variants in ABCA7, PSEN1, SORL1 and TREM2. J Neurogenet, 39 (4): 95-104. [PMID:40990081]

6. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. (2021) Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. N Engl J Med, 384 (22): 2092-2101. [PMID:33835769]

7. Ji KY, Kim SM, Yee SM, Kim MJ, Ban YJ, Kim EM, Lee EH, Choi HR, Yun H, Lee CW et al.. (2021) Cyclophilin A is an endogenous ligand for the triggering receptor expressed on myeloid cells-2 (TREM2). FASEB J, 35 (4): e21479. [PMID:33710680]

8. Joller N, Anderson AC, Kuchroo VK. (2024) LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation. Immunity, 57 (2): 206-222. [PMID:38354701]

9. Long H, Simmons A, Mayorga A, Burgess B, Nguyen T, Budda B, Rychkova A, Rhinn H, Tassi I, Ward M et al.. (2024) Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease. Alzheimers Res Ther, 16 (1): 235. [PMID:39444037]

10. Mjalli A, Andrews R, Shen J, Rothlein R. (2005) Rage antagonists as agents to reverse amyloidosis and diseases associated therewith. Patent number: US20050026811 A1. Assignee: Mjalli A, Andrews R, Shen J, Rothlein R. Priority date: 20/05/2003. Publication date: 03/02/2005.

11. Mummery CJ, Mayorga AJ, Simmons A, Chow TW, Burgess B, Nguyen T, Gao J, Budda B, Park LQ, Gupta R et al.. (2026) The TREM2 agonistic antibody AL002 in early Alzheimer's disease: a phase 2 randomized trial. Nat Med, 32 (5): 1708-1716. [PMID:41787076]

12. Nada H, El Gaamouch F, Cho S, Kuncewicz K, Calvo-Barreiro L, Gabr MT. (2025) TREM2 Activation by First-in-Class Direct Small Molecule Agonists: DEL Screening, Optimization, Biophysical Validation, and Functional Characterization. bioRxiv, Preprint. [PMID:40501642]

13. Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, Elliston K, Stern D, Shaw A. (1992) Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem, 267 (21): 14998-5004. [PMID:1378843]

14. Saeb D, Lietzke EE, Fuchs DI, Aldrich EC, Bruce KD, Sprenger KG. (2025) The flexible stalk domain of sTREM2 modulates its interactions with brain-based phospholipids. Elife, 13. [PMID:40928206]

15. Saito S, Ihara M. (2014) New therapeutic approaches for Alzheimer's disease and cerebral amyloid angiopathy. Front Aging Neurosci, 6: 290. [PMID:25368578]

16. Schlepckow K, Morenas-Rodríguez E, Hong S, Haass C. (2023) Stimulation of TREM2 with agonistic antibodies-an emerging therapeutic option for Alzheimer's disease. Lancet Neurol, 22 (11): 1048-1060. [PMID:37863592]

17. Schmidt AM, Hori O, Cao R, Yan SD, Brett J, Wautier JL, Ogawa S, Kuwabara K, Matsumoto M, Stern D. (1996) RAGE: a novel cellular receptor for advanced glycation end products. Diabetes, 45 Suppl 3: S77-80. [PMID:8674899]

18. Sharma C, Mazumder A. (2025) From Bench to Bedside: Cutting-Edge and Emerging Therapies for Alzheimer's Disease. Cent Nerv Syst Agents Med Chem, [Epub ahead of print]. [PMID:40993929]

19. Siegler JE, Klein P, Yaghi S, Vigilante N, Abdalkader M, Coutinho JM, Abdul Khalek F, Nguyen TN. (2021) Cerebral Vein Thrombosis With Vaccine-Induced Immune Thrombotic Thrombocytopenia. Stroke, 52 (9): 3045-3053. [PMID:34304601]

20. Smith CW, Montague SJ, Kardeby C, Di Y, Lowe GC, Lester WA, Watson SP, Nicolson PLR. (2021) Antiplatelet drugs block platelet activation by VITT patient serum. Blood, 138 (25): 2733-2740. [PMID:34375398]

21. Tsui JSM, Au DM, Uhm H, Wong WW, Lo RMN, Jiang Y, Ip FCF, Mok KY, Wong HY, Kwok TCY et al.. (2025) The TREM2 H157Y variant is associated with more severe neurodegeneration in Alzheimer's disease and altered immune-related processes. Alzheimers Dement, 21 (9): e70586. [PMID:40960087]

22. Yan SD, Stern D, Schmidt AM. (1997) What's the RAGE? The receptor for advanced glycation end products (RAGE) and the dark side of glucose. Eur J Clin Invest, 27 (3): 179-81. [PMID:9088851]

23. Yang H, Kim D, Yang Y, Bagyinszky E, An SSA. (2025) TREM2 in Neurodegenerative Disorders: Mutation Spectrum, Pathophysiology, and Therapeutic Targeting. Int J Mol Sci, 26 (15). [PMID:40806186]

24. Yeh FL, Wang Y, Tom I, Gonzalez LC, Sheng M. (2016) TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia. Neuron, 91 (2): 328-40. [PMID:27477018]

25. Yuan S, El Gaamouch F, Cho S, Kuncewicz K, Nada H, Gabr MT. (2025) Discovery of a Small Molecule TREM2 Agonist with Improved In Vitro Pharmacokinetic Profile and Validated Target Engagement. ACS Med Chem Lett, 16 (8): 1634-1640. [PMID:40832531]

26. Zhao Y, Wu X, Li X, Jiang LL, Gui X, Liu Y, Sun Y, Zhu B, Piña-Crespo JC, Zhang M et al.. (2018) TREM2 Is a Receptor for β-Amyloid that Mediates Microglial Function. Neuron, 97 (5): 1023-1031.e7. [PMID:29518356]

How to cite this family page

Database page citation:

Immunoglobulin like domain containing proteins. Accessed on 18/06/2026. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=984.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Gibb AJ, Kelly E, Mathie AA, Peach CJ, Veale EL, Cidlowski JA, Davenport AP, Fabbro D, Spedding M, Striessnig J, Armstrong JF, Buneman OP, Faccenda E, Harding SD, Southan C, Davies JA et al. (2025) The Concise Guide to PHARMACOLOGY 2025/26: Introduction and Other Protein Targets. Br J Pharmacol. 182: S1-S23.