KEGG   PATHWAY: ccar04350
Entry
ccar04350                   Pathway                                
Name
TGF-beta signaling pathway - Cyprinus carpio (common carp)
Description
The transforming growth factor-beta (TGF-beta) family members, which include TGF-betas, activins and bone morphogenetic proteins (BMPs), are structurally related secreted cytokines found in species ranging from worms and insects to mammals. A wide spectrum of cellular functions such as proliferation, apoptosis, differentiation and migration are regulated by TGF-beta family members. TGF-beta family member binds to the Type II receptor and recruits Type I, whereby Type II receptor phosphorylates and activates Type I. The Type I receptor, in turn, phosphorylates receptor-activated Smads ( R-Smads: Smad1, Smad2, Smad3, Smad5, and Smad8). Once phosphorylated, R-Smads associate with the co-mediator Smad, Smad4, and the heteromeric complex then translocates into the nucleus. In the nucleus, Smad complexes activate specific genes through cooperative interactions with other DNA-binding and coactivator (or co-repressor) proteins.
Class
Environmental Information Processing; Signal transduction
Pathway map
ccar04350  TGF-beta signaling pathway
ccar04350

Other DBs
GO: 0007179
Organism
Cyprinus carpio (common carp) [GN:ccar]
Gene
109044909  [KO:K16857]
109045881  smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
109045976  rhoaa; rho-related GTP-binding protein RhoA-A [KO:K04513]
109046375  ndr1; nodal homolog 2-A [KO:K04666]
109046428  [KO:K19558]
109046493  [KO:K04660]
109046637  [KO:K23096]
109046716  amh; muellerian-inhibiting factor isoform X1 [KO:K04665]
109047029  [KO:K04673] [EC:2.7.11.30]
109047131  nog5; LOW QUALITY PROTEIN: noggin 5 [KO:K04658]
109047156  lft1; lefty1 [KO:K04668]
109047284  tgfb1b; transforming growth factor beta-1 proprotein [KO:K13375]
109048016  [KO:K04382] [EC:3.1.3.16]
109048021  [KO:K03094]
109048667  [KO:K21283]
109048899  [KO:K04667]
109049134  [KO:K04678] [EC:2.3.2.26]
109049198  tgfbr1b; TGF-beta receptor type-1b [KO:K04674] [EC:2.7.11.30]
109049706  [KO:K04658]
109049707  [KO:K04658]
109049933  [KO:K19383]
109049941  [KO:K19383]
109050489  [KO:K22687]
109050630  tfr1b; transferrin receptor 1b isoform X1 [KO:K06503]
109050732  [KO:K04678] [EC:2.3.2.26]
109050853  [KO:K11644]
109050884  [KO:K06825]
109050906  [KO:K04678] [EC:2.3.2.26]
109050915  [KO:K04682]
109050933  [KO:K13568] [EC:2.7.11.30]
109051259  [KO:K16621]
109052600  [KO:K04664]
109052632  [KO:K19558]
109052994  [KO:K06766]
109053398  [KO:K04679]
109053404  [KO:K19553]
109053405  [KO:K19553]
109053450  hjv; hemojuvelin [KO:K23100]
109053615  ifng1; interferon gamma 1 precursor [KO:K04687]
109053851  [KO:K04501]
109054164  acvr1l; LOW QUALITY PROTEIN: activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
109054165  [KO:K04675] [EC:2.7.11.30]
109054182  [KO:K04661]
109054274  [KO:K04513]
109054653  ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
109055145  [KO:K13375]
109055285  [KO:K23106]
109055524  [KO:K20012]
109056171  [KO:K04676]
109056188  [KO:K23318]
109056237  [KO:K23377]
109056411  [KO:K04683]
109056978  acvr2aa; activin receptor type-2A isoform X2 [KO:K04670] [EC:2.7.11.30]
109057042  [KO:K04679]
109057215  [KO:K06067] [EC:3.5.1.98]
109057220  [KO:K04371] [EC:2.7.11.24]
109057647  [KO:K04678] [EC:2.3.2.26]
109058272  smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
109058962  bmp7b; bone morphogenetic protein 7b [KO:K16621]
109059245  [KO:K04663]
109059285  [KO:K04513]
109059580  ltbp1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
109059780  [KO:K04682]
109060158  [KO:K04666]
109060270  [KO:K13377]
109060882  [KO:K20012]
109061100  [KO:K04668]
109061332  [KO:K04498] [EC:2.3.1.48]
109061377  [KO:K04498] [EC:2.3.1.48]
109061804  [KO:K04663]
109061839  [KO:K06503]
109062782  cul1a; cullin-1a [KO:K03347]
109062788  [KO:K03347]
109062884  [KO:K04500]
109063125  [KO:K23605]
109063145  smad6a; mothers against decapentaplegic homolog 6a [KO:K04677]
109063278  [KO:K04513]
109063284  rhoac; rho-related GTP-binding protein RhoA-C [KO:K04513]
109063472  [KO:K03156]
109064245  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
109064687  [KO:K04671] [EC:2.7.11.30]
109064762  si:dkey-5i3.5; transmembrane protein 53 isoform X2 [KO:K28359]
109064774  [KO:K06847]
109065484  [KO:K13568] [EC:2.7.11.30]
109065576  [KO:K04382] [EC:3.1.3.16]
109065748  [KO:K06825]
109066065  gdf6a; growth/differentiation factor 6-A [KO:K20012]
109066102  [KO:K04671] [EC:2.7.11.30]
109066279  [KO:K04382] [EC:3.1.3.16]
109066417  [KO:K04501]
109066662  [KO:K18499]
109066711  [KO:K19410]
109067632  [KO:K11644]
109067730  [KO:K06766]
109067897  skp1; S-phase kinase-associated protein 1 [KO:K03094]
109068145  rhoab; rho-related GTP-binding protein RhoA-B [KO:K04513]
109068386  hamp; hepcidin-2 isoform X1 [KO:K23106]
109069296  [KO:K21283]
109069563  [KO:K18499]
109069649  [KO:K08121]
109069651  [KO:K08121]
109069765  [KO:K04513]
109069927  [KO:K16790]
109070464  [KO:K19559]
109070796  [KO:K26257]
109070922  [KO:K22687]
109071076  [KO:K06847]
109072288  [KO:K13596] [EC:2.7.11.30]
109072673  [KO:K03156]
109072913  ncor1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
109072918  [KO:K21283]
109072940  [KO:K04501]
109073050  [KO:K17695]
109073053  [KO:K17695]
109073132  [KO:K04666]
109073208  [KO:K17694]
109073368  [KO:K04513]
109074759  skib; v-ski avian sarcoma viral oncogene homolog b [KO:K26503]
109074762  [KO:K26503]
109074830  myca; transcriptional regulator Myc-2 isoform X1 [KO:K04377]
109074831  [KO:K04377]
109074842  [KO:K16620]
109075130  [KO:K04660]
109075712  [KO:K21283]
109076032  fstb; follistatin b [KO:K04661]
109076611  e2f5; transcription factor E2F5 [KO:K04682]
109076664  [KO:K04498] [EC:2.3.1.48]
109076699  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
109076898  tfdp1a; transcription factor Dp-1a isoform X1 [KO:K04683]
109077091  [KO:K04675] [EC:2.7.11.30]
109077094  [KO:K04500]
109079273  [KO:K04371] [EC:2.7.11.24]
109079800  [KO:K04666]
109079947  [KO:K28359]
109080732  tfr2; transferrin receptor protein 2 [KO:K23910]
109080767  [KO:K04650]
109080955  [KO:K13578] [EC:2.7.11.30]
109080982  [KO:K13578] [EC:2.7.11.30]
109081030  [KO:K04679]
109081444  [KO:K04679]
109081563  tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
109081564  [KO:K13376]
109081647  [KO:K22687]
109082100  tfa; transferrin-a [KO:K14736]
109082310  [KO:K04513]
109082424  [KO:K26257]
109082495  [KO:K04498] [EC:2.3.1.48]
109082498  rps6kb1a; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
109082561  sp1; transcription factor Sp1 isoform X1 [KO:K04684]
109082573  [KO:K04371] [EC:2.7.11.24]
109082717  [KO:K26317]
109082766  [KO:K04683]
109083059  [KO:K04661]
109083140  [KO:K04674] [EC:2.7.11.30]
109083144  [KO:K04675] [EC:2.7.11.30]
109083146  [KO:K13567] [EC:2.7.11.30]
109083597  [KO:K04682]
109083699  [KO:K04688] [EC:2.7.11.1]
109083881  [KO:K04688] [EC:2.7.11.1]
109084529  [KO:K04371] [EC:2.7.11.24]
109084573  [KO:K23318]
109084970  nog1; noggin-1 [KO:K04658]
109085882  [KO:K21283]
109086016  bmp4; bone morphogenetic protein 4 [KO:K04662]
109086023  [KO:K04671] [EC:2.7.11.30]
109086302  [KO:K06067] [EC:3.5.1.98]
109087101  [KO:K04661]
109087138  [KO:K04683]
109087320  bmp7a; bone morphogenetic protein 7a [KO:K16621]
109088001  [KO:K03456]
109088038  lrrc32; transforming growth factor beta activator LRRC32 [KO:K26316]
109088052  [KO:K08121]
109088112  [KO:K04501]
109088267  [KO:K04686]
109088268  [KO:K04686]
109088362  [KO:K13567] [EC:2.7.11.30]
109088721  [KO:K04388] [EC:2.7.11.30]
109088893  [KO:K04498] [EC:2.3.1.48]
109088895  crebbpa; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
109088965  [KO:K08121]
109089386  bmpr2b; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
109089726  [KO:K04675] [EC:2.7.11.30]
109089841  bmpr1ab; bone morphogenetic protein receptor, type IAb [KO:K04673] [EC:2.7.11.30]
109090066  inhbaa; inhibin subunit beta Aa [KO:K04667]
109090194  skilb; SKI-like proto-oncogene b [KO:K18499]
109090647  ppp2r1ba; protein phosphatase 2, regulatory subunit A, beta a [KO:K03456]
109090675  [KO:K04513]
109090805  [KO:K04501]
109091470  [KO:K23377]
109091772  [KO:K04377]
109092196  [KO:K04513]
109092301  [KO:K08121]
109092353  [KO:K10162]
109092457  [KO:K22687]
109092667  [KO:K23605]
109093589  [KO:K26257]
109093763  [KO:K04498] [EC:2.3.1.48]
109094044  [KO:K11644]
109094084  [KO:K04677]
109094138  acvr1bb; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
109094962  [KO:K26503]
109094963  [KO:K26503]
109095262  [KO:K04664]
109095610  [KO:K04513]
109096024  [KO:K04388] [EC:2.7.11.30]
109096066  [KO:K22687]
109096665  [KO:K04673] [EC:2.7.11.30]
109096833  inhbb; inhibin beta B chain [KO:K22687]
109096881  rgmd; RGM domain family, member D [KO:K23096]
109097246  [KO:K13578] [EC:2.7.11.30]
109097310  [KO:K26316]
109097403  smad9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
109097416  [KO:K16791]
109097466  [KO:K06766]
109097769  [KO:K04668]
109097820  [KO:K23605]
109098212  [KO:K04674] [EC:2.7.11.30]
109098429  [KO:K04679]
109098430  [KO:K04679]
109098476  [KO:K04685]
109098483  id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
109098485  [KO:K04680]
109098733  [KO:K06766]
109099103  [KO:K21283]
109099116  tfr1a; transferrin receptor 1a isoform X1 [KO:K06503]
109099337  [KO:K28359]
109099580  bmp6; bone morphogenetic protein 6 isoform X1 [KO:K16620]
109099669  [KO:K04658]
109100021  [KO:K04681]
109100023  [KO:K04681]
109100085  ep300a; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
109100161  [KO:K04673] [EC:2.7.11.30]
109100196  [KO:K04658]
109101640  [KO:K13376]
109101663  [KO:K26257]
109102145  [KO:K06503]
109102232  [KO:K04670] [EC:2.7.11.30]
109102288  [KO:K23100]
109102772  [KO:K10162]
109102784  tmem53; transmembrane protein 53 [KO:K28359]
109102876  [KO:K18499]
109103035  [KO:K13375]
109103189  ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
109103403  chrd; LOW QUALITY PROTEIN: chordin [KO:K04657]
109104004  [KO:K04377]
109104042  [KO:K23318]
109104067  [KO:K04501]
109104418  [KO:K04382] [EC:3.1.3.16]
109104807  [KO:K04514] [EC:2.7.11.39]
109105591  [KO:K23318]
109106189  tgfbr2b; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
109106613  [KO:K04388] [EC:2.7.11.30]
109107000  gdf7; LOW QUALITY PROTEIN: growth/differentiation factor 6-A [KO:K20013]
109107072  [KO:K17693]
109107446  [KO:K04668]
109107565  [KO:K17693]
109107997  ndr2; nodal-related 2 [KO:K04666]
109108108  [KO:K17694]
109108431  [KO:K19410]
109108576  [KO:K16857]
109108577  [KO:K16857]
109108599  [KO:K20013]
109108651  grem1b; gremlin-1 [KO:K23318]
109108703  [KO:K26317]
109109148  smad3b; mothers against decapentaplegic homolog 3b isoform X1 [KO:K23605]
109109150  smad6b; mothers against decapentaplegic homolog 6b [KO:K04677]
109109281  [KO:K21283]
109109543  [KO:K10162]
109109574  [KO:K16790]
109109954  [KO:K04501]
109109961  smad4a; LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 4a [KO:K04501]
109110013  [KO:K04514] [EC:2.7.11.39]
109110035  [KO:K23096]
109110188  [KO:K21283]
109110377  [KO:K11644]
109110444  grem2a; gremlin-2 [KO:K23318]
109111037  spaw; southpaw [KO:K04666]
109111096  [KO:K04388] [EC:2.7.11.30]
109111098  [KO:K04388] [EC:2.7.11.30]
109111629  [KO:K16622]
109111631  [KO:K16622]
109111999  [KO:K13596] [EC:2.7.11.30]
109112053  [KO:K04688] [EC:2.7.11.1]
109112702  [KO:K03156]
109112766  id2b; DNA-binding protein inhibitor ID-2b [KO:K17693]
109112774  [KO:K17693]
109112924  bmpr1bb; bone morphogenetic protein receptor, type IBb [KO:K13578] [EC:2.7.11.30]
109113365  [KO:K04657]
109113527  [KO:K04677]
109113549  [KO:K16857]
109113569  [KO:K23318]
109113570  [KO:K23318]
109113648  bmp2b; bone morphogenetic protein 2b [KO:K21283]
122135347  [KO:K03347]
122135406  [KO:K04658]
122136145  [KO:K10162]
122137016  ifng1; interferon gamma 1 isoform X1 [KO:K04687]
122138158  [KO:K03868] [EC:2.3.2.32]
122140189  [KO:K13377]
122142186  cul1b; cullin-1b [KO:K03347]
122146690  [KO:K04685]
Compound
C14819  Fe3+
Reference
PMID:12809600
  Authors
Shi Y, Massague J.
  Title
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
  Journal
Cell 113:685-700 (2003)
DOI:10.1016/S0092-8674(03)00432-X
Reference
PMID:14534577
  Authors
Derynck R, Zhang YE.
  Title
Smad-dependent and Smad-independent pathways in TGF-beta family signalling.
  Journal
Nature 425:577-84 (2003)
DOI:10.1038/nature02006
Reference
PMID:11252892
  Authors
Massague J.
  Title
How cells read TGF-beta signals.
  Journal
Nat Rev Mol Cell Biol 1:169-78 (2000)
DOI:10.1038/35043051
Reference
PMID:14557817
  Authors
Siegel PM, Massague J.
  Title
Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer.
  Journal
Nat Rev Cancer 3:807-21 (2003)
DOI:10.1038/nrc1208
Reference
PMID:14769828
  Authors
Shimasaki S, Moore RK, Otsuka F, Erickson GF.
  Title
The bone morphogenetic protein system in mammalian reproduction.
  Journal
Endocr Rev 25:72-101 (2004)
DOI:10.1210/er.2003-0007
Reference
PMID:11252746
  Authors
De Robertis EM, Larrain J, Oelgeschlager M, Wessely O.
  Title
The establishment of Spemann's organizer and patterning of the vertebrate embryo.
  Journal
Nat Rev Genet 1:171-81 (2000)
DOI:10.1038/35042039
Reference
PMID:12163231
  Authors
Gumienny TL, Padgett RW.
  Title
The other side of TGF-beta superfamily signal regulation: thinking outside the cell.
  Journal
Trends Endocrinol Metab 13:295-9 (2002)
DOI:10.1016/S1043-2760(02)00615-X
Reference
PMID:11836504
  Authors
Hamada H, Meno C, Watanabe D, Saijoh Y.
  Title
Establishment of vertebrate left-right asymmetry.
  Journal
Nat Rev Genet 3:103-13 (2002)
DOI:10.1038/nrg732
Reference
PMID:12466190
  Authors
Chang H, Brown CW, Matzuk MM.
  Title
Genetic analysis of the mammalian transforming growth factor-beta superfamily.
  Journal
Endocr Rev 23:787-823 (2002)
DOI:10.1210/er.2002-0003
Reference
PMID:10021351
  Authors
Morita K, Chow KL, Ueno N.
  Title
Regulation of body length and male tail ray pattern formation of Caenorhabditis elegans by a member of TGF-beta family.
  Journal
Development 126:1337-47 (1999)
Reference
PMID:9847239
  Authors
Krishna S, Maduzia LL, Padgett RW.
  Title
Specificity of TGFbeta signaling is conferred by distinct type I receptors and their associated SMAD proteins in Caenorhabditis elegans.
  Journal
Development 126:251-60 (1999)
Reference
PMID:15063168
  Authors
Chen Y, Mironova E, Whitaker LL, Edwards L, Yost HJ, Ramsdell AF.
  Title
ALK4 functions as a receptor for multiple TGF beta-related ligands to regulate left-right axis determination and mesoderm induction in Xenopus.
  Journal
Dev Biol 268:280-94 (2004)
DOI:10.1016/j.ydbio.2003.12.035
Reference
PMID:10519551
  Authors
Onichtchouk D, Chen YG, Dosch R, Gawantka V, Delius H, Massague J, Niehrs C
  Title
Silencing of TGF-beta signalling by the pseudoreceptor BAMBI.
  Journal
Nature 401:480-5 (1999)
DOI:10.1038/46794
Reference
PMID:19758997
  Authors
Yan X, Lin Z, Chen F, Zhao X, Chen H, Ning Y, Chen YG
  Title
Human BAMBI cooperates with Smad7 to inhibit transforming growth factor-beta signaling.
  Journal
J Biol Chem 284:30097-104 (2009)
DOI:10.1074/jbc.M109.049304
Reference
PMID:8093006
  Authors
Hildebrand A, Romaris M, Rasmussen LM, Heinegard D, Twardzik DR, Border WA, Ruoslahti E
  Title
Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta.
  Journal
Biochem J 302 ( Pt 2):527-34 (1994)
DOI:10.1042/bj3020527
Reference
PMID:10934147
  Authors
Soo C, Hu FY, Zhang X, Wang Y, Beanes SR, Lorenz HP, Hedrick MH, Mackool RJ, Plaas A, Kim SJ, Longaker MT, Freymiller E, Ting K
  Title
Differential expression of fibromodulin, a transforming growth factor-beta modulator, in fetal skin development and scarless repair.
  Journal
Am J Pathol 157:423-33 (2000)
DOI:10.1016/s0002-9440(10)64555-5
Reference
PMID:16642010
  Authors
Anderson GJ, Frazer DM
  Title
Iron metabolism meets signal transduction.
  Journal
Nat Genet 38:503-4 (2006)
DOI:10.1038/ng0506-503
Reference
PMID:26735394
  Authors
Canali S, Core AB, Zumbrennen-Bullough KB, Merkulova M, Wang CY, Schneyer AL, Pietrangelo A, Babitt JL
  Title
Activin B Induces Noncanonical SMAD1/5/8 Signaling via BMP Type I Receptors in Hepatocytes: Evidence for a Role in Hepcidin Induction by Inflammation in Male Mice.
  Journal
Endocrinology 157:1146-62 (2016)
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Ganz T, Nemeth E
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Iron homeostasis in host defence and inflammation.
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Nat Rev Immunol 15:500-10 (2015)
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PMID:15975920
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Babitt JL, Zhang Y, Samad TA, Xia Y, Tang J, Campagna JA, Schneyer AL, Woolf CJ, Lin HY
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Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic protein co-receptor.
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J Biol Chem 280:29820-7 (2005)
DOI:10.1074/jbc.M503511200
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PMID:15671031
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Samad TA, Rebbapragada A, Bell E, Zhang Y, Sidis Y, Jeong SJ, Campagna JA, Perusini S, Fabrizio DA, Schneyer AL, Lin HY, Brivanlou AH, Attisano L, Woolf CJ
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DRAGON, a bone morphogenetic protein co-receptor.
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J Biol Chem 280:14122-9 (2005)
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Vogt AS, Arsiwala T, Mohsen M, Vogel M, Manolova V, Bachmann MF
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On Iron Metabolism and Its Regulation.
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Int J Mol Sci 22:ijms22094591 (2021)
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Nat Rev Cancer 10:415-24 (2010)
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The roles and regulatory mechanisms of TGF-beta and BMP signaling in bone and cartilage development, homeostasis and disease.
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Cell Res 34:101-123 (2024)
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Related
pathway
ccar04010  MAPK signaling pathway
ccar04110  Cell cycle
ccar04120  Ubiquitin mediated proteolysis
ccar04210  Apoptosis
KO pathway
ko04350   

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