KEGG   PATHWAY: gacu04350
Entry
gacu04350                   Pathway                                
Name
TGF-beta signaling pathway - Gymnodraco acuticeps
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
gacu04350  TGF-beta signaling pathway
gacu04350

Other DBs
GO: 0007179
Organism
Gymnodraco acuticeps [GN:gacu]
Gene
117532373  [KO:K21283]
117533257  [KO:K04682]
117533379  [KO:K06067] [EC:3.5.1.98]
117533777  [KO:K13377]
117534227  [KO:K22687]
117534246  sp1; transcription factor Sp1 isoform X1 [KO:K04684]
117534559  ep300b; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
117534628  [KO:K04377]
117534632  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
117534788  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
117534919  [KO:K04501]
117535020  [KO:K04382] [EC:3.1.3.16]
117535085  tgif1; homeobox protein TGIF1 [KO:K19383]
117535136  smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
117535203  [KO:K04658]
117535346  id4; LOW QUALITY PROTEIN: DNA-binding protein inhibitor ID-4 [KO:K17695]
117535957  [KO:K03156]
117536001  [KO:K26503]
117536236  ep300a; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
117536641  gdf6b; growth/differentiation factor 6-B [KO:K20012]
117536665  bmp8a; LOW QUALITY PROTEIN: bone morphogenetic protein 8A [KO:K16622]
117536857  bmp5; bone morphogenetic protein 5 [KO:K04663]
117536909  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
117538005  [KO:K04678] [EC:2.3.2.26]
117538269  smad4a; mothers against decapentaplegic homolog 4a [KO:K04501]
117538454  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
117538718  gdf5; growth/differentiation factor 5 [KO:K04664]
117538835  smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
117538881  smad6b; mothers against decapentaplegic homolog 6b [KO:K04677]
117538911  smad3b; mothers against decapentaplegic homolog 3b [KO:K23605]
117539151  [KO:K23377]
117539163  [KO:K03347]
117539281  [KO:K04670] [EC:2.7.11.30]
117539839  nog1; noggin-1 [KO:K04658]
117539925  rbl1; LOW QUALITY PROTEIN: retinoblastoma-like protein 1 [KO:K04681]
117540167  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
117540209  skp1; S-phase kinase-associated protein 1 isoform X1 [KO:K03094]
117540596  acvr1l; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
117540770  fmodb; fibromodulin [KO:K08121]
117540892  zfyve9a; LOW QUALITY PROTEIN: zinc finger FYVE domain-containing protein 9 [KO:K04679]
117540958  si:dkey-222b8.1; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
117541390  skila; ski-like protein [KO:K18499]
117541397  bmpr1bb; bone morphogenetic protein receptor, type IBb [KO:K13578] [EC:2.7.11.30]
117541518  e2f5; transcription factor E2F5 [KO:K04682]
117541780  rhoab; rho-related GTP-binding protein RhoA-B [KO:K04513]
117541876  acvr1ba; activin A receptor type 1Ba [KO:K13567] [EC:2.7.11.30]
117541994  [KO:K26257]
117542094  acvr2ba; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
117542099  [KO:K04513]
117542219  admp; anti-dorsalizing morphogenic protein [KO:K21283]
117542385  [KO:K13596] [EC:2.7.11.30]
117542627  [KO:K04388] [EC:2.7.11.30]
117542826  e2f4; transcription factor E2F4 [KO:K04682]
117543125  bmp7b; bone morphogenetic protein 7b [KO:K16621]
117543536  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
117543575  bmp6; bone morphogenetic protein 6 isoform X1 [KO:K16620]
117543589  nrros; transforming growth factor beta activator LRRC33 [KO:K26317]
117543691  id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
117543756  [KO:K16621]
117544100  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
117544580  [KO:K04683]
117544662  myca; transcriptional regulator Myc-A [KO:K04377]
117544753  tfr1b; transferrin receptor 1b [KO:K06503]
117544938  ndr2; nodal-related 2 [KO:K04666]
117545111  nog2; noggin-2 [KO:K04658]
117545610  tfr1a; transferrin receptor 1a [KO:K06503]
117545809  si:dkey-5i3.5; transmembrane protein 53-A isoform X1 [KO:K28359]
117545976  [KO:K04513]
117546099  amh; LOW QUALITY PROTEIN: muellerian-inhibiting factor [KO:K04665]
117546171  rgmd; RGM domain family, member D [KO:K23096]
117546425  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117546599  [KO:K04671] [EC:2.7.11.30]
117546840  rgmb; RGM domain family member B [KO:K06847]
117547163  lemd3; inner nuclear membrane protein Man1 [KO:K19410]
117547528  fmoda; fibromodulin a [KO:K08121]
117547686  [KO:K04513]
117548220  [KO:K26257]
117548231  skib; v-ski avian sarcoma viral oncogene homolog b [KO:K26503]
117548406  crebbpb; CREB binding protein b isoform X1 [KO:K04498] [EC:2.3.1.48]
117549139  [KO:K04681]
117549253  thbs1b; thrombospondin-1 [KO:K16857]
117549257  fbn1; fibrillin-1 [KO:K06825]
117549267  [KO:K11644]
117549268  neo1a; neogenin 1a isoform X1 [KO:K06766]
117549316  bmp4; bone morphogenetic protein 4 [KO:K04662]
117549346  smad3a; mothers against decapentaplegic homolog 3a isoform X1 [KO:K23605]
117549441  [KO:K04677]
117549658  [KO:K14736]
117549900  id2a; DNA-binding protein inhibitor ID-2a [KO:K17693]
117549945  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
117549992  [KO:K06067] [EC:3.5.1.98]
117550045  grem1b; gremlin-1 [KO:K23318]
117550137  [KO:K16857]
117550242  bambia; BMP and activin membrane-bound inhibitor (Xenopus laevis) homolog a [KO:K10162]
117550644  ltbp1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
117550903  zfyve9b; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
117551054  [KO:K13567] [EC:2.7.11.30]
117551071  [KO:K04513]
117551121  nbl1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
117551210  lrrc32; transforming growth factor beta activator LRRC32 [KO:K26316]
117551309  zfyve16; LOW QUALITY PROTEIN: zinc finger FYVE domain-containing protein 16 [KO:K04679]
117551480  chrd; chordin [KO:K04657]
117551643  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
117552197  ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
117552291  bmp16; bone morphogenetic protein 16 [KO:K21283]
117552812  [KO:K22687]
117553293  tmem53; transmembrane protein 53 [KO:K28359]
117553449  [KO:K04673] [EC:2.7.11.30]
117553629  pitx2; pituitary homeobox 2 isoform X1 [KO:K04686]
117553895  [KO:K04388] [EC:2.7.11.30]
117554010  [KO:K23106]
117554027  [KO:K23106]
117554167  bmp2b; bone morphogenetic protein 2b [KO:K21283]
117554333  lft1; lefty1 [KO:K04668]
117554707  smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
117554725  [KO:K04671] [EC:2.7.11.30]
117554769  [KO:K04500]
117554789  ndr1; nodal-related 1 [KO:K04666]
117554891  gdf6a; growth/differentiation factor 6-A isoform X1 [KO:K20012]
117555322  cdkn2a/b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
117555508  tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
117555603  tgfb1a; transforming growth factor, beta 1a [KO:K13375]
117556011  [KO:K04382] [EC:3.1.3.16]
117556200  smad1; LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1 [KO:K04676]
117556405  id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
117556829  [KO:K04675] [EC:2.7.11.30]
117556875  [KO:K13568] [EC:2.7.11.30]
117556937  [KO:K26316]
117557203  [KO:K04682]
117557262  ncor1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
117557488  inhbab; inhibin subunit beta Ab isoform X1 [KO:K04667]
117557710  rgma; repulsive guidance molecule A [KO:K23096]
117558360  tfa; transferrin-a isoform X1 [KO:K14736]
117558492  rock1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
117558648  [KO:K04501]
117558660  [KO:K13578] [EC:2.7.11.30]
117558661  [KO:K13578] [EC:2.7.11.30]
117559137  [KO:K28359]
117559165  dcn; decorin [KO:K04660]
117559380  sin3aa; SIN3 transcription regulator family member Aa isoform X1 [KO:K11644]
117560252  [KO:K04688] [EC:2.7.11.1]
117560918  grem2a; gremlin-2 [KO:K23318]
117561098  fsta; LOW QUALITY PROTEIN: follistatin-A [KO:K04661]
117561165  spaw; southpaw [KO:K04666]
117561595  crebbpa; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
117562019  hamp; hepcidin-1 [KO:K23106]
117563082  [KO:K23318]
117563171  inhbb; inhibin beta B chain [KO:K22687]
117563185  [KO:K04678] [EC:2.3.2.26]
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)
DOI:10.1210/en.2015-1747
Reference
PMID:26160612
  Authors
Ganz T, Nemeth E
  Title
Iron homeostasis in host defence and inflammation.
  Journal
Nat Rev Immunol 15:500-10 (2015)
DOI:10.1038/nri3863
Reference
PMID:15975920
  Authors
Babitt JL, Zhang Y, Samad TA, Xia Y, Tang J, Campagna JA, Schneyer AL, Woolf CJ, Lin HY
  Title
Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic protein co-receptor.
  Journal
J Biol Chem 280:29820-7 (2005)
DOI:10.1074/jbc.M503511200
Reference
PMID:15671031
  Authors
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
  Title
DRAGON, a bone morphogenetic protein co-receptor.
  Journal
J Biol Chem 280:14122-9 (2005)
DOI:10.1074/jbc.M410034200
Reference
PMID:33925597
  Authors
Vogt AS, Arsiwala T, Mohsen M, Vogel M, Manolova V, Bachmann MF
  Title
On Iron Metabolism and Its Regulation.
  Journal
Int J Mol Sci 22:ijms22094591 (2021)
DOI:10.3390/ijms22094591
Reference
PMID:20495575
  Authors
Ikushima H, Miyazono K
  Title
TGFbeta signalling: a complex web in cancer progression.
  Journal
Nat Rev Cancer 10:415-24 (2010)
DOI:10.1038/nrc2853
Reference
PMID:38267638
  Authors
Wu M, Wu S, Chen W, Li YP
  Title
The roles and regulatory mechanisms of TGF-beta and BMP signaling in bone and cartilage development, homeostasis and disease.
  Journal
Cell Res 34:101-123 (2024)
DOI:10.1038/s41422-023-00918-9
Related
pathway
gacu04010  MAPK signaling pathway
gacu04110  Cell cycle
gacu04120  Ubiquitin mediated proteolysis
gacu04210  Apoptosis
KO pathway
ko04350   

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