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)
D13195  Usnoflast (USAN/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
10000  AKT3; RAC-gamma serine/threonine-protein kinase isoform 1 [KO:K04456] [EC:2.7.11.1]
10332  CLEC4M; C-type lectin domain family 4 member M isoform 1 [KO:K06563]
10379  IRF9; interferon regulatory factor 9 isoform 2 [KO:K04693]
10892  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform a [KO:K07369] [EC:3.4.22.-]
110117499  P3R3URF-PIK3R3; LOC110117498-PIK3R3 readthrough [KO:K02649]
114548  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform a [KO:K12800]
1147  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform 1 [KO:K04467] [EC:2.7.11.10]
1263  PLK3; serine/threonine-protein kinase PLK3 [KO:K08862] [EC:2.7.11.21]
1432  MAPK14; mitogen-activated protein kinase 14 isoform 2 [KO:K04441] [EC:2.7.11.24]
1540  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform 1 [KO:K08601] [EC:3.4.19.12]
163688  CALML6; calmodulin-like protein 6 isoform 1 [KO:K02183]
1959  EGR2; E3 SUMO-protein ligase EGR2 isoform a [KO:K12496]
1960  EGR3; early growth response protein 3 isoform 1 [KO:K12497]
207  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
208  AKT2; RAC-beta serine/threonine-protein kinase isoform 1 [KO:K04456] [EC:2.7.11.1]
2207  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma precursor [KO:K07983]
22800  RRAS2; ras-related protein R-Ras2 isoform a [KO:K07830]
22808  MRAS; ras-related protein M-Ras isoform 1 precursor [KO:K07831]
23365  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform 1 [KO:K07532]
26253  CLEC4E; C-type lectin domain family 4 member E isoform 1 [KO:K10059]
29108  PYCARD; apoptosis-associated speck-like protein containing a CARD isoform a [KO:K12799]
30835  CD209; CD209 antigen isoform 1 [KO:K06563]
3265  HRAS; GTPase HRas isoform 1 [KO:K02833]
338339  CLEC4D; C-type lectin domain family 4 member D [KO:K10058]
3551  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform 1 [KO:K07209] [EC:2.7.11.10]
3553  IL1B; interleukin-1 beta proprotein [KO:K04519]
3558  IL2; interleukin-2 precursor [KO:K05429]
3569  IL6; interleukin-6 isoform 1 precursor [KO:K05405]
3586  IL10; interleukin-10 isoform 1 precursor [KO:K05443]
3592  IL12A; interleukin-12 subunit alpha isoform 4 precursor [KO:K05406]
3593  IL12B; interleukin-12 subunit beta precursor [KO:K05425]
3659  IRF1; interferon regulatory factor 1 isoform 1 [KO:K09444]
3708  ITPR1; inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 isoform 4 [KO:K04958]
3709  ITPR2; inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 isoform 1 [KO:K04959]
3710  ITPR3; inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 [KO:K04960]
3725  JUN; transcription factor Jun [KO:K04448]
3845  KRAS; GTPase KRas isoform a [KO:K07827]
387  RHOA; transforming protein RhoA isoform 1 precursor [KO:K04513]
4046  LSP1; lymphocyte-specific protein 1 isoform 1 [KO:K14957]
4193  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform 2 [KO:K06643] [EC:2.3.2.27]
4772  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform F [KO:K04446]
4773  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform C [KO:K17332]
4775  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform 1 [KO:K17333]
4776  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform 2 [KO:K17334]
4790  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform 2 proprotein [KO:K02580]
4791  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform a [KO:K04469]
4792  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
4893  NRAS; GTPase NRas [KO:K07828]
5058  PAK1; serine/threonine-protein kinase PAK 1 isoform 2 [KO:K04409] [EC:2.7.11.1]
51266  CLEC1B; C-type lectin domain family 1 member B isoform a [KO:K10070]
51561  IL23A; interleukin-23 subunit alpha precursor [KO:K05426]
51806  CALML5; calmodulin-like protein 5 [KO:K02183]
5290  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform 1 [KO:K00922] [EC:2.7.1.153]
5295  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform 1 [KO:K02649]
5296  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
53342  IL17D; interleukin-17D isoform c precursor [KO:K05492]
5336  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
5530  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform 1 [KO:K04348] [EC:3.1.3.16]
5532  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform b [KO:K04348] [EC:3.1.3.16]
5533  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform 2 [KO:K04348] [EC:3.1.3.16]
5534  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
5535  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
5580  PRKCD; protein kinase C delta type isoform c [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 isoform 1 [KO:K04371] [EC:2.7.11.24]
5599  MAPK8; mitogen-activated protein kinase 8 isoform alpha2 [KO:K04440] [EC:2.7.11.24]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 isoform alpha2 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 isoform 1 [KO:K04440] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
5743  PTGS2; prostaglandin G/H synthase 2 precursor [KO:K11987] [EC:1.14.99.1]
5781  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform 1 [KO:K07293] [EC:3.1.3.48]
5894  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform b [KO:K04366] [EC:2.7.11.1]
5970  RELA; transcription factor p65 isoform 1 [KO:K04735]
5971  RELB; transcription factor RelB isoform 1 [KO:K09253]
602  BCL3; B-cell lymphoma 3 protein [KO:K09258]
6237  RRAS; ras-related protein R-Ras [KO:K07829]
6300  MAPK12; mitogen-activated protein kinase 12 isoform 1 [KO:K04441] [EC:2.7.11.24]
6361  CCL17; C-C motif chemokine 17 precursor [KO:K21083]
6367  CCL22; C-C motif chemokine 22 precursor [KO:K21095]
64170  CARD9; caspase recruitment domain-containing protein 9 isoform 1 [KO:K12794]
64581  CLEC7A; C-type lectin domain family 7 member A isoform a [KO:K10074]
6714  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
6772  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform alpha [KO:K11220]
6773  STAT2; signal transducer and activator of transcription 2 isoform 1 [KO:K11221]
6850  SYK; tyrosine-protein kinase SYK isoform Syk(L) [KO:K05855] [EC:2.7.10.2]
7124  TNF; tumor necrosis factor [KO:K03156]
801  CALM1; calmodulin-1 isoform 2 [KO:K02183]
805  CALM2; calmodulin-2 isoform 2 [KO:K02183]
808  CALM3; calmodulin-3 isoform 1 [KO:K02183]
810  CALML3; calmodulin-like protein 3 [KO:K02183]
834  CASP1; caspase-1 isoform alpha precursor [KO:K01370] [EC:3.4.22.36]
841  CASP8; caspase-8 isoform 2 precursor [KO:K04398] [EC:3.4.22.61]
8503  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform 1 [KO:K02649]
8517  IKBKG; NF-kappa-B essential modulator isoform a [KO:K07210]
868  CBLB; E3 ubiquitin-protein ligase CBL-B isoform b [KO:K22517] [EC:2.3.2.27]
8844  KSR1; kinase suppressor of Ras 1 isoform 2 [KO:K14958]
8915  BCL10; B-cell lymphoma/leukemia 10 isoform 1 [KO:K07368]
9020  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
91860  CALML4; calmodulin-like protein 4 isoform 1 [KO:K02183]
9261  MAPKAPK2; MAP kinase-activated protein kinase 2 isoform 2 [KO:K04443] [EC:2.7.11.1]
93978  CLEC6A; C-type lectin domain family 6 member A isoform 1 [KO:K17514]
9641  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform 1 [KO:K07211] [EC:2.7.11.10]
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   

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