CLEC10A is a type II transmembrane protein (passing one time through the membrane and oriented with the N terminus inward) that induces endocytosis after ligand binding. To release the ligand in the endosome, participating Ca2+ ions have to be unbound first. This leads to a significant increase in cytoplasmic Ca2+ concentration.[7]
CLEC10A binds most strongly to N-Acetylgalactosamine (GalNAc), preferring α-GalNAc over β-GalNAc, unmodified galactose is bound very weakly.[7] CLEC10A is the only C-type lectin within the human immune system that exclusively recognizes terminal GalNAc.[9] This includes the Tn antigen (GalNAc O-bound to serine or threonine) which is prominently expressed on carcinomas, where it can also be sialylated. These tumor-associated antigens (Neu5Acα2,6-Tn, and NeuGcα2,6-Tn) are also bound.[10]
CLEC10A has also been shown to bind GalNAc in the teichoic acid of the Staphylococcus aureus cell wall and the surface of parasites.[11][12]
CLEC10A is expressed by dendritic cells that differentiate from monocytes recruited to inflammatory environments.[13]
CD45 contains a Tn antigen in exon B. CD45 has 3 important exons (4,5,6), that are designated A,B,C. Isoforms of CD45 are labeled depending on the presence of these exons. CLEC10A can for example bind CD45RB or CD45R, which is shorthand for CD45RABC. Binding causes attenuation of T cell activity, apoptosis, and immunosuppression. However, active T cells express shorter isoforms of CD45 (CD45RO, CD45RA) that lack exon B.[7]
CLEC10A signalling induces IL-10 production in dendritic cells, in part through increasing intracellular Ca2+ concentration. IL-10 is the main regulatory and anti-inflammatory cytokine produced in humans. In contrast, low concentrations of intracellular Ca2+ result in production of IL-12, a pro-inflammatory cytokine that also leads to Th1 polarisation.[7]
In cancer research, CLEC10A expression was found to both improve[14][15][16] and worsen[17] survival.
In animal models, deficiency of the orthologue to CLEC10A, Mgl1 is associated with worse outcomes in infection and excessive inflammation.[18]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000132514 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000000318 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Suzuki N, Yamamoto K, Toyoshima S, Osawa T, Irimura T (January 1996). "Molecular cloning and expression of cDNA encoding human macrophage C-type lectin. Its unique carbohydrate binding specificity for Tn antigen". Journal of Immunology. 156 (1): 128–135. doi:10.4049/jimmunol.156.1.128. PMID 8598452. S2CID 25597354.
^Heger L, Balk S, Lühr JJ, Heidkamp GF, Lehmann CH, Hatscher L, et al. (2018-04-27). "CLEC10A Is a Specific Marker for Human CD1c+ Dendritic Cells and Enhances Their Toll-Like Receptor 7/8-Induced Cytokine Secretion". Frontiers in Immunology. 9: 744. doi:10.3389/fimmu.2018.00744. PMC5934495. PMID 29755453.
^ abcdeHoober JK (July 2020). "ASGR1 and Its Enigmatic Relative, CLEC10A". International Journal of Molecular Sciences. 21 (14): 4818. doi:10.3390/ijms21144818. PMC7404283. PMID 32650396.
^Zelensky AN, Gready JE (December 2005). "The C-type lectin-like domain superfamily". The FEBS Journal. 272 (24): 6179–6217. doi:10.1111/j.1742-4658.2005.05031.x. PMID 16336259. S2CID 7084402.
^van Kooyk Y, Ilarregui JM, van Vliet SJ (February 2015). "Novel insights into the immunomodulatory role of the dendritic cell and macrophage-expressed C-type lectin MGL". Immunobiology. 220 (2): 185–192. doi:10.1016/j.imbio.2014.10.002. PMID 25454488. S2CID 32172457.
^Mortezai N, Behnken HN, Kurze AK, Ludewig P, Buck F, Meyer B, Wagener C (July 2013). "Tumor-associated Neu5Ac-Tn and Neu5Gc-Tn antigens bind to C-type lectin CLEC10A (CD301, MGL)". Glycobiology. 23 (7): 844–852. doi:10.1093/glycob/cwt021. PMID 23507963.
^Mnich ME, van Dalen R, Gerlach D, Hendriks A, Xia G, Peschel A, et al. (October 2019). "The C-type lectin receptor MGL senses N-acetylgalactosamine on the unique Staphylococcus aureus ST395 wall teichoic acid". Cellular Microbiology. 21 (10): e13072. doi:10.1111/cmi.13072. PMC6771913. PMID 31219660.
^van Vliet SJ, van Liempt E, Saeland E, Aarnoudse CA, Appelmelk B, Irimura T, et al. (May 2005). "Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells". International Immunology. 17 (5): 661–669. doi:10.1093/intimm/dxh246. PMID 15802303.
^Tang-Huau TL, Gueguen P, Goudot C, Durand M, Bohec M, Baulande S, et al. (July 2018). "Human in vivo-generated monocyte-derived dendritic cells and macrophages cross-present antigens through a vacuolar pathway". Nature Communications. 9 (1): 2570. Bibcode:2018NatCo...9.2570T. doi:10.1038/s41467-018-04985-0. PMC6028641. PMID 29967419.
^Kurze AK, Buhs S, Eggert D, Oliveira-Ferrer L, Müller V, Niendorf A, et al. (August 2019). "Immature O-glycans recognized by the macrophage glycoreceptor CLEC10A (MGL) are induced by 4-hydroxy-tamoxifen, oxidative stress and DNA-damage in breast cancer cells". Cell Communication and Signaling. 17 (1): 107. doi:10.1186/s12964-019-0420-9. PMC6712659. PMID 31455323.
^Eggink LL, Roby KF, Cote R, Kenneth Hoober J (April 2018). "An innovative immunotherapeutic strategy for ovarian cancer: CLEC10A and glycomimetic peptides". Journal for Immunotherapy of Cancer. 6 (1): 28. doi:10.1186/s40425-018-0339-5. PMC5905120. PMID 29665849.
^Qin Y, Wang L, Zhang L, Li J, Liao L, Huang L, et al. (2021). "Immunological role and prognostic potential of CLEC10A in pan-cancer". American Journal of Translational Research. 14 (5): 2844–2860. doi:10.2139/ssrn.3932103. PMC9185031. PMID 35702069. S2CID 242193292.
^Dusoswa SA, Verhoeff J, Abels E, Méndez-Huergo SP, Croci DO, Kuijper LH, et al. (February 2020). "Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin". Proceedings of the National Academy of Sciences of the United States of America. 117 (7): 3693–3703. Bibcode:2020PNAS..117.3693D. doi:10.1073/pnas.1907921117. PMC7035608. PMID 32019882.
^Jondle CN, Sharma A, Simonson TJ, Larson B, Mishra BB, Sharma J (April 2016). "Macrophage Galactose-Type Lectin-1 Deficiency Is Associated with Increased Neutrophilia and Hyperinflammation in Gram-Negative Pneumonia". Journal of Immunology. 196 (7): 3088–3096. doi:10.4049/jimmunol.1501790. PMC4936400. PMID 26912318.
External linksedit
Human CLEC10A genome location and CLEC10A gene details page in the UCSC Genome Browser.
Further readingedit
Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
van Vliet SJ, Steeghs L, Bruijns SC, Vaezirad MM, Snijders Blok C, Arenas Busto JA, et al. (October 2009). Seifert HS (ed.). "Variation of Neisseria gonorrhoeae lipooligosaccharide directs dendritic cell-induced T helper responses". PLOS Pathogens. 5 (10): e1000625. doi:10.1371/journal.ppat.1000625. PMC2757725. PMID 19834553.
Iijima M, Tomita M, Morozumi S, Kawagashira Y, Nakamura T, Koike H, et al. (October 2009). "Single nucleotide polymorphism of TAG-1 influences IVIg responsiveness of Japanese patients with CIDP". Neurology. 73 (17): 1348–1352. doi:10.1212/WNL.0b013e3181bd1139. PMID 19776380. S2CID 207116106.
clec10a, type, lectin, domain, family, member, also, designated, cd301, protein, that, humans, encoded, gene, part, type, lectin, superfamily, binds, acetylgalactosamine, galnac, mainly, expressed, myeloid, cells, also, oocytes, very, early, stages, embryogene. C type lectin domain family 10 member A CLEC10A also designated as CD301 is a protein that in humans is encoded by the CLEC10A gene 5 CLEC10A is part of the C type lectin superfamily and binds to N Acetylgalactosamine GalNAc It is mainly expressed on myeloid cells and also on oocytes and very early stages of embryogenesis CLEC10A is used as a marker of the CD1c dendritic cell subgroup also called cDC2 6 The actions of CLEC10A are diverse depending on the ligand and environment 7 CLEC10AIdentifiersAliasesCLEC10A CD301 CLECSF13 CLECSF14 HML HML2 MGL C type lectin domain family 10 member A C type lectin domain containing 10AExternal IDsOMIM 605999 MGI 96975 HomoloGene 7836 GeneCards CLEC10AGene location Human Chr Chromosome 17 human 1 Band17p13 1Start7 074 537 bp 1 End7 080 307 bp 1 Gene location Mouse Chr Chromosome 11 mouse 2 Band11 B3 11 42 99 cMStart70 047 023 bp 2 End70 061 660 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inoocytesecondary oocytemonocyteright coronary arterygallbladderappendixrectumlymph nodesmooth muscle tissuebloodTop expressed inwhite adipose tissuesubcutaneous adipose tissuemammary glandlipsciatic nervecervixskin of backanklesecondary oocyteintercostal muscleMore reference expression dataBioGPSn aGene ontologyMolecular functioncarbohydrate bindingCellular componentintegral component of membrane plasma membrane membraneBiological processinnate immune response endocytosis adaptive immune response immune system process stimulatory C type lectin receptor signaling pathwaySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez1046217312EnsemblENSG00000132514ENSMUSG00000000318UniProtQ8IUN9P49300RefSeq mRNA NM 006344NM 182906NM 001330070NM 001204252NM 010796RefSeq protein NP 001316999NP 006335NP 878910NP 001191181NP 034926Location UCSC Chr 17 7 07 7 08 MbChr 11 70 05 70 06 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 References 3 External links 4 Further readingFunction editGenerally C type lectins bind carbohydrate moieties usually in the presence of Ca2 and have diverse functions such as cell adhesion cell cell signalling glycoprotein turnover and roles in inflammation and immune response 8 CLEC10A is a type II transmembrane protein passing one time through the membrane and oriented with the N terminus inward that induces endocytosis after ligand binding To release the ligand in the endosome participating Ca2 ions have to be unbound first This leads to a significant increase in cytoplasmic Ca2 concentration 7 CLEC10A binds most strongly to N Acetylgalactosamine GalNAc preferring a GalNAc over b GalNAc unmodified galactose is bound very weakly 7 CLEC10A is the only C type lectin within the human immune system that exclusively recognizes terminal GalNAc 9 This includes the Tn antigen GalNAc O bound to serine or threonine which is prominently expressed on carcinomas where it can also be sialylated These tumor associated antigens Neu5Aca2 6 Tn and NeuGca2 6 Tn are also bound 10 CLEC10A has also been shown to bind GalNAc in the teichoic acid of the Staphylococcus aureus cell wall and the surface of parasites 11 12 CLEC10A is expressed by dendritic cells that differentiate from monocytes recruited to inflammatory environments 13 CD45 contains a Tn antigen in exon B CD45 has 3 important exons 4 5 6 that are designated A B C Isoforms of CD45 are labeled depending on the presence of these exons CLEC10A can for example bind CD45RB or CD45R which is shorthand for CD45RABC Binding causes attenuation of T cell activity apoptosis and immunosuppression However active T cells express shorter isoforms of CD45 CD45RO CD45RA that lack exon B 7 CLEC10A signalling induces IL 10 production in dendritic cells in part through increasing intracellular Ca2 concentration IL 10 is the main regulatory and anti inflammatory cytokine produced in humans In contrast low concentrations of intracellular Ca2 result in production of IL 12 a pro inflammatory cytokine that also leads to Th1 polarisation 7 In cancer research CLEC10A expression was found to both improve 14 15 16 and worsen 17 survival In animal models deficiency of the orthologue to CLEC10A Mgl1 is associated with worse outcomes in infection and excessive inflammation 18 References edit a b c GRCh38 Ensembl release 89 ENSG00000132514 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000000318 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Suzuki N Yamamoto K Toyoshima S Osawa T Irimura T January 1996 Molecular cloning and expression of cDNA encoding human macrophage C type lectin Its unique carbohydrate binding specificity for Tn antigen Journal of Immunology 156 1 128 135 doi 10 4049 jimmunol 156 1 128 PMID 8598452 S2CID 25597354 Heger L Balk S Luhr JJ Heidkamp GF Lehmann CH Hatscher L et al 2018 04 27 CLEC10A Is a Specific Marker for Human CD1c Dendritic Cells and Enhances Their Toll Like Receptor 7 8 Induced Cytokine Secretion Frontiers in Immunology 9 744 doi 10 3389 fimmu 2018 00744 PMC 5934495 PMID 29755453 a b c d e Hoober JK July 2020 ASGR1 and Its Enigmatic Relative CLEC10A International Journal of Molecular Sciences 21 14 4818 doi 10 3390 ijms21144818 PMC 7404283 PMID 32650396 Zelensky AN Gready JE December 2005 The C type lectin like domain superfamily The FEBS Journal 272 24 6179 6217 doi 10 1111 j 1742 4658 2005 05031 x PMID 16336259 S2CID 7084402 van Kooyk Y Ilarregui JM van Vliet SJ February 2015 Novel insights into the immunomodulatory role of the dendritic cell and macrophage expressed C type lectin MGL Immunobiology 220 2 185 192 doi 10 1016 j imbio 2014 10 002 PMID 25454488 S2CID 32172457 Mortezai N Behnken HN Kurze AK Ludewig P Buck F Meyer B Wagener C July 2013 Tumor associated Neu5Ac Tn and Neu5Gc Tn antigens bind to C type lectin CLEC10A CD301 MGL Glycobiology 23 7 844 852 doi 10 1093 glycob cwt021 PMID 23507963 Mnich ME van Dalen R Gerlach D Hendriks A Xia G Peschel A et al October 2019 The C type lectin receptor MGL senses N acetylgalactosamine on the unique Staphylococcus aureus ST395 wall teichoic acid Cellular Microbiology 21 10 e13072 doi 10 1111 cmi 13072 PMC 6771913 PMID 31219660 van Vliet SJ van Liempt E Saeland E Aarnoudse CA Appelmelk B Irimura T et al May 2005 Carbohydrate profiling reveals a distinctive role for the C type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells International Immunology 17 5 661 669 doi 10 1093 intimm dxh246 PMID 15802303 Tang Huau TL Gueguen P Goudot C Durand M Bohec M Baulande S et al July 2018 Human in vivo generated monocyte derived dendritic cells and macrophages cross present antigens through a vacuolar pathway Nature Communications 9 1 2570 Bibcode 2018NatCo 9 2570T doi 10 1038 s41467 018 04985 0 PMC 6028641 PMID 29967419 Kurze AK Buhs S Eggert D Oliveira Ferrer L Muller V Niendorf A et al August 2019 Immature O glycans recognized by the macrophage glycoreceptor CLEC10A MGL are induced by 4 hydroxy tamoxifen oxidative stress and DNA damage in breast cancer cells Cell Communication and Signaling 17 1 107 doi 10 1186 s12964 019 0420 9 PMC 6712659 PMID 31455323 Eggink LL Roby KF Cote R Kenneth Hoober J April 2018 An innovative immunotherapeutic strategy for ovarian cancer CLEC10A and glycomimetic peptides Journal for Immunotherapy of Cancer 6 1 28 doi 10 1186 s40425 018 0339 5 PMC 5905120 PMID 29665849 Qin Y Wang L Zhang L Li J Liao L Huang L et al 2021 Immunological role and prognostic potential of CLEC10A in pan cancer American Journal of Translational Research 14 5 2844 2860 doi 10 2139 ssrn 3932103 PMC 9185031 PMID 35702069 S2CID 242193292 Dusoswa SA Verhoeff J Abels E Mendez Huergo SP Croci DO Kuijper LH et al February 2020 Glioblastomas exploit truncated O linked glycans for local and distant immune modulation via the macrophage galactose type lectin Proceedings of the National Academy of Sciences of the United States of America 117 7 3693 3703 Bibcode 2020PNAS 117 3693D doi 10 1073 pnas 1907921117 PMC 7035608 PMID 32019882 Jondle CN Sharma A Simonson TJ Larson B Mishra BB Sharma J April 2016 Macrophage Galactose Type Lectin 1 Deficiency Is Associated with Increased Neutrophilia and Hyperinflammation in Gram Negative Pneumonia Journal of Immunology 196 7 3088 3096 doi 10 4049 jimmunol 1501790 PMC 4936400 PMID 26912318 External links editHuman CLEC10A genome location and CLEC10A gene details page in the UCSC Genome Browser Further reading editBonaldo MF Lennon G Soares MB September 1996 Normalization and subtraction two approaches to facilitate gene discovery Genome Research 6 9 791 806 doi 10 1101 gr 6 9 791 PMID 8889548 van Vliet SJ Steeghs L Bruijns SC Vaezirad MM Snijders Blok C Arenas Busto JA et al October 2009 Seifert HS ed Variation of Neisseria gonorrhoeae lipooligosaccharide directs dendritic cell induced T helper responses PLOS Pathogens 5 10 e1000625 doi 10 1371 journal ppat 1000625 PMC 2757725 PMID 19834553 Iijima M Tomita M Morozumi S Kawagashira Y Nakamura T Koike H et al October 2009 Single nucleotide polymorphism of TAG 1 influences IVIg responsiveness of Japanese patients with CIDP Neurology 73 17 1348 1352 doi 10 1212 WNL 0b013e3181bd1139 PMID 19776380 S2CID 207116106 This article incorporates text from the United States National Library of Medicine which is in the public domain Retrieved from https en wikipedia org w index php title CLEC10A amp oldid 1195777374, wikipedia, wiki, book, books, library,
