CLEC1B

Last updated
CLEC1B
Protein CLEC1B PDB 2c6u.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CLEC1B , 1810061I13Rik, CLEC2, CLEC2B, PRO1384, QDED721, C-type lectin domain family 1 member B
External IDs OMIM: 606783; MGI: 1913287; HomoloGene: 49468; GeneCards: CLEC1B; OMA:CLEC1B - orthologs
Orthologs
SpeciesHumanMouse
Entrez

51266

56760

Ensembl

ENSG00000165682

ENSMUSG00000030159

UniProt

Q9P126

Q9JL99

RefSeq (mRNA)

NM_001099431
NM_016509
NM_001393342

NM_001204239
NM_001204253
NM_019985

RefSeq (protein)

NP_001092901
NP_057593

NP_001191168
NP_001191182
NP_064369

Location (UCSC) Chr 12: 9.99 – 10.01 Mb Chr 6: 129.37 – 129.39 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

C-type lectin domain family 1 member B (also termed CLEC-1b, C-type lectin-like receptor 2, CLEC-2, CLEC2, CLEC2B, PRO1384, QDED721, C-type lectin domain family 1 member B, CLEC1B, activation-induced C-type lectin, AICL, and 1810061I13Rik) is a cell surface receptor protein. It binds certain biomolecules that act as ligands that when bound to the CLEC-1b expressed by cells stimulates certain functions in these cells. The human CLEC-1b receptor is encoded by the CLEC1B gene which is located on the short (i.e., "p")-arm of chromosome 12 at region 1, band 3, sub-band 1 to sub-band 2 (position notated as 12p13.31-p13.2).<https://www.ncbi.nlm.nih.gov/gene/387836> Most of the recent literature terms the C-type lectin domain family 1 member B as CLEC-2. [5] [6] [7] [8] [9] [10] Since current reports commonly use CLEC-2 rather than CLEC-1b, CLEC-2 will be used here in place of CLEC1b in further describing this protein.

Contents

CLEC-2 is a member of the broad family of pattern recognition receptors (i.e., PRRs). Vertebrate PRRs can be classified into five types based on their structural similarities: a) toll-like receptors, b) NOD-like receptors, c) RIG-I-like receptors, d) AIM2 (also termed absent in melanoma 2 or interferon-inducible protein AIM2), and e) C-type lectin receptors (i.e., CLR). [11] [12] CLRs are a superfamily of more than 1,000 proteins. They are subdivided into 17 subgroups. All members of this family possess one or more C-type lectin-like domains, i.e., protein domains that have a characteristic loop-in-a-loop structure formed by their amino acid sequences which form a large loop that encloses a smaller, internal loop or some other type of secondary structure. These internal loops or other structures are formed by two disulfide bridges located at the bases of these loops. [13] . CLEC-2 is a C-type lectin receptor. [14]

Agents activating CLEC-2

While podoplanin is the most studied activator of CLEC-2, CLEC-2 is also activated by: rhodocytin (a platelet-activating snake venom also termed aggretin); hemin (an iron-containing porphyrin containing chlorine); galectin-9; the human immunodeficiency virus (which causes the acquired immunodeficiency syndrome, i.e. AIDs); dextran sulfate; sulfated polysaccharides; fucoidan (a long chain sulfated polysaccharide found in various species of brown algae); katacine (an extract of the Polygonaceae family of flowering plants); S100A13 (i.e., S100 calcium-binding protein A13); humsn CLEC7A (also termed C-type lectin domain family 7 member A or dectin-1); and the soot, carbon, and other particles in the exhaust gas of diesel engines. [12] [15] [16] [17]

Cells expressing CLEC-2

CLEC-2 is highly expressed on mouse and human platelets as well as megakaryocytes, i.e., platelet-forming cells. [18] [19] It is also expressed on the surface membranes of myeloid cells (i.e., a broad category of blood cells that originate from hematopoietic stem cells in the bone marrow and differentiate into NK cells, B cells [8] [20] ; platelets, dendritic cells, [21] follicular dendritic cells, mesothelial cells (i.e., simple squamous epithelial cells of mesodermal origin in the mesothelium), epithelial cells in lymphatic vessels, and cancer-associated fibroblasts (i.e., non-malignant fibroblasts that are located in cancer tissues). [22]

Functions of activated CLEC-2

Podoplanin activation of CLEC-2

Based primarily on preclinical studies done in rodents, podoplanin-induced activation of CLEC-2 (see the podoplanin page for details): a) on megakaryocytes promotes their production of platelets; [16] [23] [24] b) ischemia/reperfusion tissue damage, [25] [26] [27] cancer-associated venous thromboembolisms, atherosclerosis, [16] [28] [26] and regeneration of the liver after 70% of it is removed experimentally; [12] [29] and c) on the platelets of fetuses in order for them to develop normal normal blood vessels, lymphatic vessels, the heart [24] , and lung. [30]

S100A13 activation of CLEC-2

Studies in isolated human and mouse aortas and mice strongly suggest that the S100A13 expressed on the surface of smooth muscle cells is responsible for activating platelets and causing thrombus formation during the early stages of thrombus formation before podoplanin is expressed. [11] [16] [31]

C-type lectin domain family 7 member A activation of CLEC-2

Studies in various cultured cell systems indicate that the CLEC7A (i.e., C-type lectin domain family 7 member protein, also termed dectin-1) from humans (sometimes notated as hdectin-1) as well as the dectin-1 proteins isolated from the cells of higher primates activate human as well as mouse CLEC-2. However, the CLEC7A protein isolated from mouse cells (sometimes notated as mdectin-1) does not activate human or mouse CLEC-2. [17] A structurally similar protein, CLEC6A (i.e., C-type lectin domain containing 6A, also termed dectin-2) has a very different set of actions and does not activate CLEC-2. CLEC7A (i.e., dectin-1) in humans is expressed on the surface membranes of vascular endothelial cells, tissue dendritic cells, tissue macrophages, and circulating white blood cells such as neutrophils, monocytes, and circulating dendritic cells. [11] [17] CLEC7A identifies and interacts with various fungi (e.g., yeast, Candida albicans, Pneumocystis jirovecii and Aspergillus species to promote immune responses against these pathogens. CLEC7A also stimulates isolated human platelets and mouse platelets made to express human CLEC-2 but not mouse platelets expressing mouse CLEC-2. Further studies in mice made to express human CLEC-2 in place of mouse CLEC2 were found to stimulate platelets without triggering venous thromboses whereas podoplanin triggered both platelet activation and venous thromboses. These latter findings suggest that CLEC7A is a comparatively moderate antihemorrhagic agent (i.e., inhibitor of bleeding) which may control physiological processes through platelets thrombosis-independent mechanisms. Further studies may show that CLEC-2 is useful for inhibiting bleeding without causing thrombosis. [17] [32]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000165682 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030159 – 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. ↑ Colonna M, Samaridis J, Angman L (Mar 2000). "Molecular characterization of two novel C-type lectin-like receptors, one of which is selectively expressed in human dendritic cells". Eur J Immunol. 30 (2): 697–704. doi: 10.1002/1521-4141(200002)30:2<697::AID-IMMU697>3.0.CO;2-M . PMID   10671229.
  6. ↑ Sobanov Y, Bernreiter A, Derdak S, Mechtcheriakova D, Schweighofer B, Duchler M, Kalthoff F, Hofer E (Dec 2001). "A novel cluster of lectin-like receptor genes expressed in monocytic, dendritic and endothelial cells maps close to the NK receptor genes in the human NK gene complex". Eur J Immunol. 31 (12): 3493–503. doi:10.1002/1521-4141(200112)31:12<3493::AID-IMMU3493>3.0.CO;2-9. PMID   11745369. S2CID   42415487.
  7. ↑ "Entrez Gene: CLEC1B C-type lectin domain family 1, member B".
  8. 1 2 Meng D, Luo M, Liu B (2021). "The Role of CLEC-2 and Its Ligands in Thromboinflammation". Frontiers in Immunology. 12 688643. doi: 10.3389/fimmu.2021.688643 . PMC   8220156 . PMID   34177942.
  9. ↑ Li X, Tao X, Ding X (August 2022). "An integrative analysis to reveal that CLEC2B and ferroptosis may bridge the gap between psoriatic arthritis and cancer development". Scientific Reports. 12 (1) 14653. Bibcode:2022NatSR..1214653L. doi:10.1038/s41598-022-19135-2. PMC   9420124 . PMID   36030279.
  10. ↑ Jing Q, Yuan C, Zhou C, Jin W, Wang A, Wu Y, Shang W, Zhang G, Ke X, Du J, Li Y, Shao F (June 2023). "Comprehensive analysis identifies CLEC1B as a potential prognostic biomarker in hepatocellular carcinoma". Cancer Cell Interna-tional. 23 (1) 113. doi: 10.1186/s12935-023-02939-1 . PMC   10262401 . PMID   37308868.
  11. 1 2 3 Li D, Wu M (August 2021). "Pattern recognition receptors in health and diseases". Signal Transduction and Targeted Therapy. 6 (1) 291. doi:10.1038/s41392-021-00687-0. PMC   8333067 . PMID   34344870.
  12. 1 2 3 Sun L, Wang Z, Liu Z, Mu G, Cui Y, Xiang Q (March 2024). "C-type lectin-like receptor 2: roles and drug target". Thrombosis Journal. 22 (1) 27. doi: 10.1186/s12959-024-00594-8 . PMC   10949654 . PMID   38504248.
  13. ↑ Zelensky AN, Gready JE (December 2005). "The C-type lectin-like domain superfamily". The FEBS Journal. 272 (24): 6179–217. doi:10.1111/j.1742-4658.2005.05031.x. PMID   16336259.
  14. ↑ Reis e Sousa C, Yamasaki S, Brown GD (April 2024). "Myeloid C-type lectin receptors in innate immune recognition". Immunity. 57 (4): 700–717. doi:10.1016/j.immuni.2024.03.005. PMID   38599166.
  15. ↑ Morán LA, Di Y, Sowa MA, Hermida-Nogueira L, Barrachina MN, Martin E, Clark JC, Mize TH, Eble JA, Moreira D, Pollitt AY, Loza MI, Domínguez E, Watson SP, García Á (August 2022). "Katacine Is a New Ligand of CLEC-2 that Acts as a Platelet Agonist". Thrombosis and Haemostasis. 122 (8): 1361–1368. doi:10.1055/a-1772-1069. PMC   9393086 . PMID   35170009.
  16. 1 2 3 4 Inoue O, Hokamura K, Shirai T, Osada M, Tsukiji N, Hatakeyama K, Umemura K, Asada Y, Suzuki-Inoue K, Ozaki Y (2015). "Vascular Smooth Muscle Cells Stimulate Platelets and Facilitate Thrombus Formation through Platelet CLEC-2: Implications in Atherothrombosis". PLOS ONE. 10 (9) e0139357. Bibcode:2015PLoSO..1039357I. doi: 10.1371/journal.pone.0139357 . PMC   4587843 . PMID   26418160.
  17. 1 2 3 4 Haji S, Ito T, Guenther C, Nakano M, Shimizu T, Mori D, Chiba Y, Tanaka M, Mishra SK, Willment JA, Brown GD, Nagae M, Yamasaki S (December 2022). "Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2". eLife. 11 e83037. doi: 10.7554/eLife.83037 . PMC   9788829 . PMID   36479973.
  18. ↑ Nakamura-Ishizu A, Takubo K, Kobayashi H, Suzuki-Inoue K, Suda T (November 2015). "CLEC-2 in megakaryocytes is critical for maintenance of hematopoietic stem cells in the bone marrow". The Journal of Experimental Medicine. 212 (12): 2133–46. doi:10.1084/jem.20150057. PMC   4647260 . PMID   26552707.
  19. ↑ Mourão-Sá D, Robinson MJ, Zelenay S, Sancho D, Chakravarty P, Larsen R, Plantinga M, Van Rooijen N, Soares MP, Lambrecht B, Reis e Sousa C (October 2011). "CLEC-2 signaling via Syk in myeloid cells can regulate inflammatory responses". European Journal of Immunology. 41 (10): 3040–53. doi:10.1002/eji.201141641. PMID   21728173.
  20. ↑ Kerrigan AM, Dennehy KM, Mourão-Sá D, Faro-Trindade I, Willment JA, Taylor PR, Eble JA, Reis e Sousa C, Brown GD (April 2009). "CLEC-2 is a phagocytic activation receptor expressed on murine peripheral blood neutrophils". Journal of Immunology (Baltimore, Md. : 1950). 182 (7): 4150–7. doi:10.4049/jimmunol.0802808. PMC   2727695 . PMID   19299712.
  21. ↑ Krishnan H, Rayes J, Miyashita T, Ishii G, Retzbach EP, Sheehan SA, Takemoto A, Chang YW, Yoneda K, Asai J, Jensen L, Chalise L, Natsume A, Goldberg GS (May 2018). "Podoplanin: An emerging cancer biomarker and therapeutic target". Cancer Science. 109 (5): 1292–1299. doi:10.1111/cas.13580. PMC   5980289 . PMID   29575529.
  22. ↑ Agrawal S, Ganguly S, Hajian P, Cao JN, Agrawal A (October 2015). "PDGF upregulates CLEC-2 to induce T regulatory cells". Oncotarget. 6 (30): 28621–32. doi:10.18632/oncotarget.5765. PMC   4745681 . PMID   26416420.
  23. ↑ Wang Y, Peng D, Huang Y, Cao Y, Li H, Zhang X (2022). "Podoplanin: Its roles and functions in neurological diseases and brain cancers". Frontiers in Pharmacology. 13 964973. doi: 10.3389/fphar.2022.964973 . PMC   9514838 . PMID   36176432.
  24. 1 2 Suzuki-Inoue K, Tsukiji N (May 2024). "A role of platelet C-type lectin-like receptor-2 and its ligand podoplanin in vascular biology". Current Opinion in Hematology. 31 (3): 130–139. doi:10.1097/MOH.0000000000000805. PMID   38359177.
  25. ↑ Cheok YY, Tan GM, Chan YT, Abdullah S, Looi CY, Wong WF (December 2024). "Podoplanin and its multifaceted roles in mammalian developmental program". Cells & Development. 180 203943. doi:10.1016/j.cdev.2024.203943. PMID   39111713.
  26. 1 2 Huang Y, Lu M, Wang Y, Zhang C, Cao Y, Zhang X (2023). "Podoplanin: A potential therapeutic target for thrombotic diseases". Frontiers in Neurology. 14 1118843. doi: 10.3389/fneur.2023.1118843 . PMC   10033871 . PMID   36970507.
  27. ↑ Meng D, Ma X, Li H, Wu X, Cao Y, Miao Z, Zhang X (April 2021). "A Role of the Podoplanin-CLEC-2 Axis in Promoting Inflammatory Response After Ischemic Stroke in Mice". Neurotoxicity Research. 39 (2): 477–488. doi:10.1007/s12640-020-00295-w. PMID   33165736.
  28. ↑ Furukoji E, Yamashita A, Nakamura K, Hirai T, Asada Y (November 2019). "Podoplanin expression on endothelial cells promotes superficial erosive injury and thrombus formation in rat carotid artery: Implications for plaque erosion". Thrombosis Research. 183: 76–79. doi:10.1016/j.thromres.2019.10.015. PMID   31670230.
  29. ↑ Kono H, Fujii H, Suzuki-Inoue K, Inoue O, Furuya S, Hirayama K, Akazawa Y, Nakata Y, Sun C, Tsukiji N, Shirai T, Ozaki Y (May 2017). "The platelet-activating receptor C-type lectin receptor-2 plays an essential role in liver regeneration after partial hepatectomy in mice". Journal of Thrombosis and Haemostasis. 15 (5): 998–1008. doi: 10.1111/jth.13672 . PMID   28294559.
  30. ↑ Tsukiji N, Inoue O, Morimoto M, Tatsumi N, Nagatomo H, Ueta K, Shirai T, Sasaki T, Otake S, Tamura S, Tachibana T, Okabe M, Hirashima M, Ozaki Y, Suzuki-Inoue K (September 2018). "Platelets play an essential role in murine lung development through Clec-2/podoplanin interaction". Blood. 132 (11): 1167–1179. doi:10.1182/blood-2017-12-823369. PMID   29853539.
  31. ↑ Ozaki Y, Tamura S, Suzuki-Inoue K (2016). "New horizon in platelet function: with special reference to a recently-found molecule, CLEC-2". Thrombosis Journal. 14 (Suppl 1) 27. doi: 10.1186/s12959-016-0099-8 . PMC   5056494 . PMID   27766053.
  32. ↑ Lefèbre J, Falk T, Ning Y, Rademacher C (May 2024). "Secondary Sites of the C-type Lectin-Like Fold". Chemistry (Weinheim an der Bergstrasse, Germany). 30 (30) e202400660. doi:10.1002/chem.202400660. PMID   38527187.

See also

Podoplanin

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