KEGG   PATHWAY: hsa04625
hsa04625                    Pathway                                
C-type lectin receptor signaling pathway - Homo sapiens (human)
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.
Organismal Systems; Immune system
Pathway map
hsa04625  C-type lectin receptor signaling pathway

D12237  Zunsemetinib (USAN)
D12422  Selnoflast (USAN/INN)
D12423  Selnoflast potassium (USAN)
D12720  Nibrozetone (USAN)
Homo sapiens (human) [GN:hsa]
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:]
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:]
5781  PTPN11; protein tyrosine phosphatase non-receptor type 11 [KO:K07293] [EC:]
9020  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:]
1147  CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:]
4791  NFKB2; nuclear factor kappa B subunit 2 [KO:K04469]
5336  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:]
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:]
5532  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:]
5533  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:]
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:]
5580  PRKCD; protein kinase C delta [KO:K06068] [EC:]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
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:]
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:]
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:]
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:]
6300  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:]
1432  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:]
3725  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
868  CBLB; Cbl proto-oncogene B [KO:K22517] [EC:]
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:]
8844  KSR1; kinase suppressor of ras 1 [KO:K14958]
1263  PLK3; polo like kinase 3 [KO:K08862] [EC:]
6714  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:]
9641  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:]
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:]
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:]
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:]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:]
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:]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:]
4193  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:]
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]
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  Trehalose dimycolate
C21791  Rhodocytin
G13115  Mannose-capped lipoarabinomannan
Geijtenbeek TB, Gringhuis SI
C-type lectin receptors in the control of T helper cell differentiation.
Nat Rev Immunol 16:433-48 (2016)
Hajishengallis G, Lambris JD
Microbial manipulation of receptor crosstalk in innate immunity.
Nat Rev Immunol 11:187-200 (2011)
Iliev ID, Leonardi I
Fungal dysbiosis: immunity and interactions at mucosal barriers.
Nat Rev Immunol 17:635-646 (2017)
Richardson MB, Williams SJ
MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns.
Front Immunol 5:288 (2014)
Vautier S, MacCallum DM, Brown GD
C-type lectin receptors and cytokines in fungal immunity.
Cytokine 58:89-99 (2012)
Gauglitz GG, Callenberg H, Weindl G, Korting HC
Host defence against Candida albicans and the role of pattern-recognition receptors.
Acta Derm Venereol 92:291-8 (2012)
Cunha C, Carvalho A, Esposito A, Bistoni F, Romani L
DAMP signaling in fungal infections and diseases.
Front Immunol 3:286 (2012)
Tang J, Lin G, Langdon WY, Tao L, Zhang J
Regulation of C-Type Lectin Receptor-Mediated Antifungal Immunity.
Front Immunol 9:123 (2018)
Mayer S, Raulf MK, Lepenies B
C-type lectins: their network and roles in pathogen recognition and immunity.
Histochem Cell Biol 147:223-237 (2017)
Plato A, Willment JA, Brown GD
C-type lectin-like receptors of the dectin-1 cluster: ligands and signaling pathways.
Int Rev Immunol 32:134-56 (2013)
Dupaul-Chicoine J, Saleh M
A new path to IL-1beta production controlled by caspase-8.
Nat Immunol 13:211-2 (2012)
Batbayar S, Lee DH, Kim HW
Immunomodulation of Fungal beta-Glucan in Host Defense Signaling by Dectin-1.
Biomol Ther (Seoul) 20:433-45 (2012)
Bendickova K, Tidu F, Fric J
Calcineurin-NFAT signalling in myeloid leucocytes: new prospects and pitfalls in immunosuppressive therapy.
EMBO Mol Med 9:990-999 (2017)
den Dunnen J, Gringhuis SI, Geijtenbeek TB
Innate signaling by the C-type lectin DC-SIGN dictates immune responses.
Cancer Immunol Immunother 58:1149-57 (2009)
Marakalala MJ, Ndlovu H
Signaling C-type lectin receptors in antimycobacterial immunity.
PLoS Pathog 13:e1006333 (2017)
Gringhuis SI, Kaptein TM, Wevers BA, Mesman AW, Geijtenbeek TB
Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKKepsilon- and CYLD-dependent Bcl3 activation.
Nat Commun 5:3898 (2014)
Geijtenbeek TB, Gringhuis SI
Signalling through C-type lectin receptors: shaping immune responses.
Nat Rev Immunol 9:465-79 (2009)
Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Wevers B, Bruijns SC, Geijtenbeek TB
Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk.
Nat Immunol 10:203-13 (2009)
hsa04658  Th1 and Th2 cell differentiation
hsa04659  Th17 cell differentiation
KO pathway

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