KEGG   PATHWAY: hhip04350
Entry
hhip04350                   Pathway                                
Name
TGF-beta signaling pathway - Hippoglossus hippoglossus (Atlantic halibut)
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
hhip04350  TGF-beta signaling pathway
hhip04350

Other DBs
GO: 0007179
Organism
Hippoglossus hippoglossus (Atlantic halibut) [GN:hhip]
Gene
117752426  nog2; noggin-2 [KO:K04658]
117752626  nog3; noggin-3 [KO:K04658]
117752834  [KO:K21283]
117752911  ndr2; nodal-related 2 [KO:K04666]
117753189  ep300a; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
117753418  [KO:K04682]
117753552  [KO:K03347]
117753891  bmp6; bone morphogenetic protein 6 [KO:K16620]
117753906  inhbaa; inhibin subunit beta Aa [KO:K04667]
117753981  tgfbr1b; TGF-beta receptor type-1b [KO:K04674] [EC:2.7.11.30]
117753998  nrros; transforming growth factor beta activator LRRC33 [KO:K26317]
117754035  bambia; BMP and activin membrane-bound inhibitor (Xenopus laevis) homolog a [KO:K10162]
117754048  tgif1; homeobox protein TGIF1 [KO:K19383]
117754053  myca; transcriptional regulator Myc-A isoform X1 [KO:K04377]
117754186  tfr1b; transferrin receptor 1b [KO:K06503]
117754276  [KO:K13596] [EC:2.7.11.30]
117754491  tgfbr2l; LOW QUALITY PROTEIN: TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
117754571  fbn1; fibrillin-1 isoform X1 [KO:K06825]
117754867  acvr2aa; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
117754909  [KO:K04675] [EC:2.7.11.30]
117754928  [KO:K04671] [EC:2.7.11.30]
117754984  tfdp1a; transcription factor Dp-1a isoform X1 [KO:K04683]
117755125  [KO:K13568] [EC:2.7.11.30]
117755158  inhbb; inhibin beta B chain [KO:K22687]
117755594  [KO:K11644]
117755695  neo1a; neogenin 1a isoform X1 [KO:K06766]
117755864  id2a; DNA-binding protein inhibitor ID-2a [KO:K17693]
117755904  id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
117755995  [KO:K16857]
117756327  bmp4; bone morphogenetic protein 4 [KO:K04662]
117756333  smad3a; mothers against decapentaplegic homolog 3a [KO:K23605]
117756578  grem1b; gremlin-1 [KO:K23318]
117756595  [KO:K06067] [EC:3.5.1.98]
117756644  tgfb3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
117756783  acvr1l; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
117757282  dcn; decorin [KO:K04660]
117757458  [KO:K28359]
117757579  lemd3; inner nuclear membrane protein Man1 [KO:K19410]
117758206  [KO:K06067] [EC:3.5.1.98]
117758316  lft1; lefty1 [KO:K04668]
117758338  thbs1b; thrombospondin-1 [KO:K16857]
117758516  [KO:K13377]
117758548  bmp2b; bone morphogenetic protein 2b [KO:K21283]
117758605  grem1a; gremlin-1a [KO:K23318]
117759146  [KO:K23377]
117759573  [KO:K04677]
117759618  [KO:K04681]
117759717  [KO:K04678] [EC:2.3.2.26]
117760068  amh; muellerian-inhibiting factor [KO:K04665]
117760441  rgmd; RGM domain family, member D [KO:K23096]
117760489  zfyve9b; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
117761126  skib; v-ski avian sarcoma viral oncogene homolog b [KO:K26503]
117761250  id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
117761295  [KO:K13567] [EC:2.7.11.30]
117761398  crebbpa; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
117761543  [KO:K26257]
117761588  mych; myelocytomatosis oncogene homolog [KO:K04377]
117761652  rhoca; ras homolog family member Ca [KO:K04513]
117761850  [KO:K04513]
117761853  nbl1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
117761878  [KO:K22687]
117761907  sp1; transcription factor Sp1 isoform X1 [KO:K04684]
117762106  zgc:113307; lumican [KO:K08121]
117762107  fmoda; fibromodulin a [KO:K08121]
117762180  gdf5; growth/differentiation factor 5 isoform X1 [KO:K04664]
117762217  rbl1; retinoblastoma-like protein 1 [KO:K04681]
117762293  [KO:K19553]
117762299  [KO:K16621]
117762530  adamtsl7; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
117762777  e2f4; transcription factor E2F4 [KO:K04682]
117763103  smad6b; mothers against decapentaplegic homolog 6b [KO:K04677]
117763294  rgma; repulsive guidance molecule A [KO:K23096]
117763390  si:dkey-5i3.5; uncharacterized protein si:dkey-5i3.5 [KO:K28359]
117763466  smad3b; mothers against decapentaplegic homolog 3b [KO:K23605]
117763648  sin3aa; SIN3 transcription regulator family member Aa isoform X1 [KO:K11644]
117764033  [KO:K04513]
117764034  [KO:K04513]
117764388  acvr1ba; activin A receptor type 1Ba [KO:K13567] [EC:2.7.11.30]
117764762  fmodb; fibromodulin [KO:K08121]
117764865  bmp7b; bone morphogenetic protein 7b isoform X1 [KO:K16621]
117764960  emp3b; epithelial membrane protein 3b [KO:K26257]
117765043  [KO:K04688] [EC:2.7.11.1]
117765120  skia; v-ski avian sarcoma viral oncogene homolog a [KO:K26503]
117765171  [KO:K04513]
117765178  [KO:K04513]
117765316  rhoab; rho-related GTP-binding protein RhoA-B [KO:K04513]
117765838  cdkn2a/b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
117765862  [KO:K04658]
117766207  ep300b; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
117766232  smurf2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
117766234  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
117766292  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
117766747  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
117766859  crebbpb; CREB binding protein b isoform X1 [KO:K04498] [EC:2.3.1.48]
117767253  rgmb; RGM domain family member B [KO:K06847]
117767308  [KO:K04501]
117767563  fsta; follistatin-A isoform X1 [KO:K04661]
117767605  bmpr1ba; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
117767782  [KO:K04500]
117767997  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117768386  [KO:K04382] [EC:3.1.3.16]
117768499  spaw; southpaw [KO:K04666]
117768915  [KO:K26316]
117769402  [KO:K04382] [EC:3.1.3.16]
117769434  smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
117769598  pitx2; LOW QUALITY PROTEIN: pituitary homeobox 2 [KO:K04686]
117769623  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
117770418  hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
117770903  [KO:K04388] [EC:2.7.11.30]
117770963  bmp8a; bone morphogenetic protein 8A [KO:K16622]
117770968  gdf6b; growth/differentiation factor 6-B [KO:K20012]
117771112  si:dkey-222b8.1; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
117771451  [KO:K04666]
117771484  smad4a; mothers against decapentaplegic homolog 4a [KO:K04501]
117771516  bmpr1bb; bone morphogenetic protein receptor, type IBb isoform X1 [KO:K13578] [EC:2.7.11.30]
117771681  smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
117771721  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
117771800  zfyve16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
117771820  smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
117772384  tgfb1a; transforming growth factor, beta 1a isoform X1 [KO:K13375]
117772697  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
117772763  ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
117772981  bmp16; bone morphogenetic protein 16 [KO:K21283]
117773183  chrd; chordin [KO:K04657]
117773841  lrrc32; transforming growth factor beta activator LRRC32 isoform X1 [KO:K26316]
117774017  ncor1; LOW QUALITY PROTEIN: nuclear receptor corepressor 1 [KO:K04650]
117774035  [KO:K04671] [EC:2.7.11.30]
117774099  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
117774290  skp1; S-phase kinase-associated protein 1 [KO:K03094]
117774459  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
117774576  smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
117775037  [KO:K04673] [EC:2.7.11.30]
117775288  ltbp1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
117775548  grem2a; gremlin-2 [KO:K23318]
117775983  bmp5; bone morphogenetic protein 5 [KO:K04663]
117776118  [KO:K04670] [EC:2.7.11.30]
117776460  [KO:K23106]
117776488  hjv; hemojuvelin [KO:K23100]
117776628  [KO:K04501]
117776949  gdf6a; growth/differentiation factor 6-A [KO:K20012]
117777013  [KO:K23106]
117777014  [KO:K23106]
117777015  [KO:K23106]
117777016  [KO:K23106]
117777017  [KO:K23106]
117777108  tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
117777178  [KO:K04388] [EC:2.7.11.30]
117777240  id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
117777469  hamp; hepcidin-1 [KO:K23106]
117777543  [KO:K22687]
117777649  zfyve9a; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
117777701  rock1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
117778092  tfr1a; transferrin receptor 1a isoform X1 [KO:K06503]
117778096  acvr2ba; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
117778230  admp; anti-dorsalizing morphogenic protein [KO:K21283]
117778311  inhbab; inhibin subunit beta Ab [KO:K04667]
117778501  tfa; transferrin-a [KO:K14736]
117778675  tmem53; transmembrane protein 53 [KO:K28359]
117778681  e2f5; transcription factor E2F5 [KO:K04682]
117778854  skila; LOW QUALITY PROTEIN: ski-like protein [KO:K18499]
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
hhip04010  MAPK signaling pathway
hhip04110  Cell cycle
hhip04120  Ubiquitin mediated proteolysis
hhip04210  Apoptosis
KO pathway
ko04350   

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