KEGG   PATHWAY: pcad04625
Entry
pcad04625                   Pathway                                
Name
C-type lectin receptor signaling pathway - Physeter catodon (sperm whale)
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
pcad04625  C-type lectin receptor signaling pathway
pcad04625

Organism
Physeter catodon (sperm whale) [GN:pcad]
Gene
102974795  C-type lectin domain family 7 member A isoform X1 [KO:K10074]
102975821  LSP1; lymphocyte-specific protein 1 isoform X9 [KO:K14957]
102994715  HRAS; GTPase HRas isoform X2 [KO:K02833]
102977125  KRAS; GTPase KRas isoform X1 [KO:K07827]
102992439  LOW QUALITY PROTEIN: GTPase NRas-like [KO:K07828]
102982641  NRAS; LOW QUALITY PROTEIN: GTPase NRas [KO:K07828]
102974392  MRAS; ras-related protein M-Ras [KO:K07831]
102986000  RRAS; ras-related protein R-Ras [KO:K07829]
102980435  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
102987866  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
102974198  RELA; transcription factor p65 isoform X1 [KO:K04735]
102977853  RELB; transcription factor RelB [KO:K09253]
102982335  IL12A; interleukin-12 subunit alpha [KO:K05406]
102980587  IL12B; interleukin-12 subunit beta [KO:K05425]
102994188  IL1B; interleukin-1 beta [KO:K04519]
102993186  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
102979922  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
102987506  tyrosine-protein phosphatase non-receptor type 11-like isoform X1 [KO:K07293] [EC:3.1.3.48]
102991269  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
102977668  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X2 [KO:K04467] [EC:2.7.11.10]
102983621  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X2 [KO:K04469]
102983230  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
102984842  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102992034  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
102976671  CALM1; calmodulin-1 [KO:K02183]
102988232  calmodulin-alpha [KO:K02183]
102996886  calmodulin-1-like [KO:K02183]
102993731  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
102988309  CALM3; calmodulin-3 [KO:K02183]
102977506  uncharacterized protein LOC102977506 [KO:K02183]
129392645  neo-calmodulin-like [KO:K02183]
102994784  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
102973173  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
102990815  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X8 [KO:K04348] [EC:3.1.3.16]
112065477  PPP3R2; LOW QUALITY PROTEIN: calcineurin subunit B type 2 [KO:K06268]
112067521  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
114484431  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
102988344  nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
102993777  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X5 [KO:K17332]
102984161  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
102985343  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334]
102990654  IL2; interleukin-2 [KO:K05429]
102973585  IL10; interleukin-10 [KO:K05443]
102984978  EGR2; E3 SUMO-protein ligase EGR2 isoform X1 [KO:K12496]
102976508  EGR3; early growth response protein 3 isoform X1 [KO:K12497]
102982708  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
102984279  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
102984305  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102989074  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102976103  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
102986634  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
102995954  LOW QUALITY PROTEIN: apoptosis-associated speck-like protein containing a CARD [KO:K12799]
102982110  CASP1; caspase-1 [KO:K01370] [EC:3.4.22.36]
102983532  CARD9; caspase recruitment domain-containing protein 9 isoform X3 [KO:K12794]
102993070  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
102979605  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [KO:K07369] [EC:3.4.22.-]
102988082  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
114485485  NF-kappa-B essential modulator-like isoform X1 [KO:K07210]
102980964  IKBKG; NF-kappa-B essential modulator [KO:K07210]
102976706  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102973672  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102981135  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102983069  TNF; tumor necrosis factor [KO:K03156]
102980126  IL6; interleukin-6 [KO:K05405]
102981863  IL23A; interleukin-23 subunit alpha [KO:K05426]
102977531  MAPK12; mitogen-activated protein kinase 12 isoform X3 [KO:K04441] [EC:2.7.11.24]
102989111  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102990302  MAPK13; mitogen-activated protein kinase 13 isoform X3 [KO:K04441] [EC:2.7.11.24]
102977994  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
102996353  MAPK8; mitogen-activated protein kinase 8 isoform X3 [KO:K04440] [EC:2.7.11.24]
102977417  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102984741  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102975458  JUN; transcription factor Jun [KO:K04448]
102980192  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
102989924  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
102993603  CD209; CD209 antigen [KO:K06563]
102996900  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
102983639  RHOA; transforming protein RhoA [KO:K04513]
102992923  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
102978005  LOW QUALITY PROTEIN: serine/threonine-protein kinase PAK 1-like [KO:K04409] [EC:2.7.11.1]
102989994  KSR1; kinase suppressor of Ras 1 [KO:K14958]
102990542  PLK3; serine/threonine-protein kinase PLK3 [KO:K08862] [EC:2.7.11.21]
102983882  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
102994478  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
102977655  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
102992486  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
102981574  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
112065399  IL17D; interleukin-17D [KO:K05492]
102991203  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
102976757  BCL3; B-cell lymphoma 3 protein [KO:K09258]
102992954  CCL22; C-C motif chemokine 22 [KO:K21095]
102974346  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
102984423  CLEC4E; C-type lectin domain family 4 member E [KO:K10059]
102986098  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102978952  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102977108  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102975555  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102991779  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102991192  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102981524  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102976971  AKT3; RAC-gamma serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
102990087  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102980125  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
102982890  IRF1; interferon regulatory factor 1 isoform X1 [KO:K09444]
102984140  CLEC4D; C-type lectin domain family 4 member D [KO:K10058]
102975859  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
pcad04658  Th1 and Th2 cell differentiation
pcad04659  Th17 cell differentiation
KO pathway
ko04625   
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