KEGG   PATHWAY: hsa04625
Entry
hsa04625                    Pathway                                
Name
C-type lectin receptor signaling pathway - Homo sapiens (human)
Description
C-type lectin receptors (CLRs) are a large superfamily of proteins characterized by the presence of one or more C-type lectin-like domains (CTLDs). CLRs function as pattern-recognition receptors (PRRs) for pathogen-derived ligands in dendric cells, macrophages, neutrophils, etc., such as Dectin-1 and Dectin-2 for recognition of fungi-derived B-glucan and high mannose-type carbohydrates. Upon ligand binding, CLRs stimulate intracellular signaling cascades that induce the production of inflammatory cytokines and chemokines, consequently triggering innate and adaptive immunity to pathogens.
Class
Organismal Systems; Immune system
Pathway map
hsa04625  C-type lectin receptor signaling pathway
hsa04625

Drug
D12237  Zunsemetinib (USAN)
D12422  Selnoflast (USAN/INN)
D12423  Selnoflast potassium (USAN)
D12720  Nibrozetone (USAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
64581  CLEC7A; C-type lectin domain containing 7A [KO:K10074]
4046  LSP1; lymphocyte specific protein 1 [KO:K14957]
3265  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
3845  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
4893  NRAS; NRAS proto-oncogene, GTPase [KO:K07828]
22808  MRAS; muscle RAS oncogene homolog [KO:K07831]
6237  RRAS; RAS related [KO:K07829]
22800  RRAS2; RAS related 2 [KO:K07830]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5970  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
5971  RELB; RELB proto-oncogene, NF-kB subunit [KO:K09253]
3592  IL12A; interleukin 12A [KO:K05406]
3593  IL12B; interleukin 12B [KO:K05425]
3553  IL1B; interleukin 1 beta [KO:K04519]
6850  SYK; spleen associated tyrosine kinase [KO:K05855] [EC:2.7.10.2]
5781  PTPN11; protein tyrosine phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
9020  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
1147  CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10]
4791  NFKB2; nuclear factor kappa B subunit 2 [KO:K04469]
5336  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
3708  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
3709  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
3710  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
810  CALML3; calmodulin like 3 [KO:K02183]
805  CALM2; calmodulin 2 [KO:K02183]
808  CALM3; calmodulin 3 [KO:K02183]
801  CALM1; calmodulin 1 [KO:K02183]
163688  CALML6; calmodulin like 6 [KO:K02183]
51806  CALML5; calmodulin like 5 [KO:K02183]
91860  CALML4; calmodulin like 4 [KO:K02183]
5530  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
5532  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
5533  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
5534  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
5535  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
4772  NFATC1; nuclear factor of activated T cells 1 [KO:K04446]
4773  NFATC2; nuclear factor of activated T cells 2 [KO:K17332]
4775  NFATC3; nuclear factor of activated T cells 3 [KO:K17333]
4776  NFATC4; nuclear factor of activated T cells 4 [KO:K17334]
3558  IL2; interleukin 2 [KO:K05429]
3586  IL10; interleukin 10 [KO:K05443]
1959  EGR2; early growth response 2 [KO:K12496]
1960  EGR3; early growth response 3 [KO:K12497]
5743  PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
5580  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114548  NLRP3; NLR family pyrin domain containing 3 [KO:K12800]
29108  PYCARD; PYD and CARD domain containing [KO:K12799]
834  CASP1; caspase 1 [KO:K01370] [EC:3.4.22.36]
64170  CARD9; caspase recruitment domain family member 9 [KO:K12794]
8915  BCL10; BCL10 immune signaling adaptor [KO:K07368]
10892  MALT1; MALT1 paracaspase [KO:K07369] [EC:3.4.22.-]
841  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
8517  IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210]
3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
4792  NFKBIA; NFKB inhibitor alpha [KO:K04734]
4790  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
7124  TNF; tumor necrosis factor [KO:K03156]
3569  IL6; interleukin 6 [KO:K05405]
51561  IL23A; interleukin 23 subunit alpha [KO:K05426]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
3725  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
868  CBLB; Cbl proto-oncogene B [KO:K22517] [EC:2.3.2.27]
93978  CLEC6A; C-type lectin domain containing 6A [KO:K17514]
2207  FCER1G; Fc epsilon receptor Ig [KO:K07983]
10332  CLEC4M; C-type lectin domain family 4 member M [KO:K06563]
30835  CD209; CD209 molecule [KO:K06563]
23365  ARHGEF12; Rho guanine nucleotide exchange factor 12 [KO:K07532]
387  RHOA; ras homolog family member A [KO:K04513]
5058  PAK1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1]
8844  KSR1; kinase suppressor of ras 1 [KO:K14958]
1263  PLK3; polo like kinase 3 [KO:K08862] [EC:2.7.11.21]
6714  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
9641  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
6772  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
10379  IRF9; interferon regulatory factor 9 [KO:K04693]
6773  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
53342  IL17D; interleukin 17D [KO:K05492]
1540  CYLD; CYLD lysine 63 deubiquitinase [KO:K08601] [EC:3.4.19.12]
602  BCL3; BCL3 transcription coactivator [KO:K09258]
6361  CCL17; C-C motif chemokine ligand 17 [KO:K21083]
6367  CCL22; C-C motif chemokine ligand 22 [KO:K21095]
9261  MAPKAPK2; MAPK activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
26253  CLEC4E; C-type lectin domain family 4 member E [KO:K10059]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
4193  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
3659  IRF1; interferon regulatory factor 1 [KO:K09444]
338339  CLEC4D; C-type lectin domain family 4 member D [KO:K10058]
51266  CLEC1B; C-type lectin domain family 1 member B [KO:K10070]
Compound
C00027  Hydrogen peroxide
C00076  Calcium cation
C00159  D-Mannose
C00165  Diacylglycerol
C00584  Prostaglandin E2
C00965  1,3-beta-D-Glucan
C01019  L-Fucose
C01245  D-myo-Inositol 1,4,5-trisphosphate
C16844  Hydroxyl radical
C21790  Mycobacterial trehalose dimycolate
C21791  Rhodocytin
G13115  Mannose-capped lipoarabinomannan
Reference
PMID:27291962
  Authors
Geijtenbeek TB, Gringhuis SI
  Title
C-type lectin receptors in the control of T helper cell differentiation.
  Journal
Nat Rev Immunol 16:433-48 (2016)
DOI:10.1038/nri.2016.55
Reference
PMID:21350579
  Authors
Hajishengallis G, Lambris JD
  Title
Microbial manipulation of receptor crosstalk in innate immunity.
  Journal
Nat Rev Immunol 11:187-200 (2011)
DOI:10.1038/nri2918
Reference
PMID:28604735
  Authors
Iliev ID, Leonardi I
  Title
Fungal dysbiosis: immunity and interactions at mucosal barriers.
  Journal
Nat Rev Immunol 17:635-646 (2017)
DOI:10.1038/nri.2017.55
Reference
PMID:25002863
  Authors
Richardson MB, Williams SJ
  Title
MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns.
  Journal
Front Immunol 5:288 (2014)
DOI:10.3389/fimmu.2014.00288
Reference
PMID:21924922
  Authors
Vautier S, MacCallum DM, Brown GD
  Title
C-type lectin receptors and cytokines in fungal immunity.
  Journal
Cytokine 58:89-99 (2012)
DOI:10.1016/j.cyto.2011.08.031
Reference
PMID:22170181
  Authors
Gauglitz GG, Callenberg H, Weindl G, Korting HC
  Title
Host defence against Candida albicans and the role of pattern-recognition receptors.
  Journal
Acta Derm Venereol 92:291-8 (2012)
DOI:10.2340/00015555-1250
Reference
PMID:22973279
  Authors
Cunha C, Carvalho A, Esposito A, Bistoni F, Romani L
  Title
DAMP signaling in fungal infections and diseases.
  Journal
Front Immunol 3:286 (2012)
DOI:10.3389/fimmu.2012.00286
Reference
PMID:29449845
  Authors
Tang J, Lin G, Langdon WY, Tao L, Zhang J
  Title
Regulation of C-Type Lectin Receptor-Mediated Antifungal Immunity.
  Journal
Front Immunol 9:123 (2018)
DOI:10.3389/fimmu.2018.00123
Reference
PMID:27999992
  Authors
Mayer S, Raulf MK, Lepenies B
  Title
C-type lectins: their network and roles in pathogen recognition and immunity.
  Journal
Histochem Cell Biol 147:223-237 (2017)
DOI:10.1007/s00418-016-1523-7
Reference
PMID:23570314
  Authors
Plato A, Willment JA, Brown GD
  Title
C-type lectin-like receptors of the dectin-1 cluster: ligands and signaling pathways.
  Journal
Int Rev Immunol 32:134-56 (2013)
DOI:10.3109/08830185.2013.777065
Reference
PMID:22344277
  Authors
Dupaul-Chicoine J, Saleh M
  Title
A new path to IL-1beta production controlled by caspase-8.
  Journal
Nat Immunol 13:211-2 (2012)
DOI:10.1038/ni.2241
Reference
PMID:24009832
  Authors
Batbayar S, Lee DH, Kim HW
  Title
Immunomodulation of Fungal beta-Glucan in Host Defense Signaling by Dectin-1.
  Journal
Biomol Ther (Seoul) 20:433-45 (2012)
DOI:10.4062/biomolther.2012.20.5.433
Reference
PMID:28606994
  Authors
Bendickova K, Tidu F, Fric J
  Title
Calcineurin-NFAT signalling in myeloid leucocytes: new prospects and pitfalls in immunosuppressive therapy.
  Journal
EMBO Mol Med 9:990-999 (2017)
DOI:10.15252/emmm.201707698
Reference
PMID:18998127
  Authors
den Dunnen J, Gringhuis SI, Geijtenbeek TB
  Title
Innate signaling by the C-type lectin DC-SIGN dictates immune responses.
  Journal
Cancer Immunol Immunother 58:1149-57 (2009)
DOI:10.1007/s00262-008-0615-1
Reference
PMID:28640912
  Authors
Marakalala MJ, Ndlovu H
  Title
Signaling C-type lectin receptors in antimycobacterial immunity.
  Journal
PLoS Pathog 13:e1006333 (2017)
DOI:10.1371/journal.ppat.1006333
Reference
PMID:24867235
  Authors
Gringhuis SI, Kaptein TM, Wevers BA, Mesman AW, Geijtenbeek TB
  Title
Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKKepsilon- and CYLD-dependent Bcl3 activation.
  Journal
Nat Commun 5:3898 (2014)
DOI:10.1038/ncomms4898
Reference
PMID:19521399
  Authors
Geijtenbeek TB, Gringhuis SI
  Title
Signalling through C-type lectin receptors: shaping immune responses.
  Journal
Nat Rev Immunol 9:465-79 (2009)
DOI:10.1038/nri2569
Reference
PMID:19122653
  Authors
Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Wevers B, Bruijns SC, Geijtenbeek TB
  Title
Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk.
  Journal
Nat Immunol 10:203-13 (2009)
DOI:10.1038/ni.1692
Related
pathway
hsa04658  Th1 and Th2 cell differentiation
hsa04659  Th17 cell differentiation
KO pathway
ko04625   

  All links  
Genome (1)   
   KEGG GENOME (1)   
Gene (104)   
   KEGG GENES (104)   
All databases (105)   

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