KEGG   PATHWAY: oor04350
Entry
oor04350                    Pathway                                
Name
TGF-beta signaling pathway - Orcinus orca (killer whale)
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
oor04350  TGF-beta signaling pathway
oor04350

Other DBs
GO: 0007179
Organism
Orcinus orca (killer whale) [GN:oor]
Gene
101275288  CHRD; chordin isoform X2 [KO:K04657]
101274263  NOG; noggin [KO:K04658]
101284668  NBL1; neuroblastoma suppressor of tumorigenicity 1 isoform X2 [KO:K19558]
101289084  GREM1; gremlin-1 [KO:K23318]
101283920  THBS1; thrombospondin-1 [KO:K16857]
101269874  DCN; decorin [KO:K04660]
101287433  FMOD; fibromodulin [KO:K08121]
101286797  left-right determination factor 2 [KO:K04668]
101287638  left-right determination factor 2-like isoform X1 [KO:K04668]
101281095  FST; follistatin isoform X1 [KO:K04661]
101269813  BMP2; bone morphogenetic protein 2 [KO:K21283]
101278431  BMP4; bone morphogenetic protein 4 [KO:K04662]
101284701  BMP6; bone morphogenetic protein 6 [KO:K16620]
101279483  INHBB; inhibin beta B chain [KO:K22687]
101273038  TF; serotransferrin [KO:K14736]
101272786  inhibitor of carbonic anhydrase [KO:K14736]
101271997  BMP5; bone morphogenetic protein 5 [KO:K04663]
101283186  BMP7; bone morphogenetic protein 7 isoform X2 [KO:K16621]
101287790  BMP8A; bone morphogenetic protein 8A [KO:K16622]
105747843  bone morphogenetic protein 8B [KO:K16622]
101285606  GDF5; growth/differentiation factor 5 [KO:K04664]
101283244  GDF6; growth/differentiation factor 6 [KO:K20012]
101281504  GDF7; growth/differentiation factor 7 [KO:K20013]
101280977  AMH; muellerian-inhibiting factor [KO:K04665]
101282933  IFNG; interferon gamma [KO:K04687]
101269870  TNF; tumor necrosis factor [KO:K03156]
101275022  THSD4; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
101290335  FBN1; fibrillin-1 [KO:K06825]
101288387  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
101286197  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
101276254  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
101289027  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
101273061  INHBA; inhibin beta A chain [KO:K04667]
101276532  INHBC; inhibin beta C chain [KO:K22688]
101276778  INHBE; inhibin beta E chain [KO:K22689]
101289673  NODAL; nodal homolog [KO:K04666]
101283235  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
101287667  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
101285877  ACVR1; activin receptor type-1 isoform X2 [KO:K04675] [EC:2.7.11.30]
101276638  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
101283151  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
101284981  HJV; hemojuvelin isoform X1 [KO:K23100]
101279480  NEO1; neogenin isoform X6 [KO:K06766]
101278165  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
101278154  TFR2; transferrin receptor protein 2 isoform X5 [KO:K23910]
101275788  TFRC; transferrin receptor protein 1 isoform X2 [KO:K06503]
101284587  RGMA; repulsive guidance molecule A isoform X2 [KO:K23096]
101285040  RGMB; repulsive guidance molecule B [KO:K06847]
101284253  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
101287555  TGFBR1; TGF-beta receptor type-1 isoform X2 [KO:K04674] [EC:2.7.11.30]
101289351  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
101271358  EMP3; epithelial membrane protein 3 [KO:K26257]
101286222  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
101272882  NRROS; transforming growth factor beta activator LRRC33 isoform X2 [KO:K26317]
101273958  ACVR1B; activin receptor type-1B isoform X8 [KO:K13567] [EC:2.7.11.30]
101277282  ACVR2B; activin receptor type-2B isoform X2 [KO:K13596] [EC:2.7.11.30]
101286390  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
101281468  IGSF1; immunoglobulin superfamily member 1 [KO:K26168]
101270314  BAMBI; BMP and activin membrane-bound inhibitor homolog isoform X1 [KO:K10162]
101288860  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
101270415  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
101280698  SMAD9; mothers against decapentaplegic homolog 9 [KO:K16791]
101278299  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
101288074  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
101285250  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
101287825  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
101279368  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
101285547  E3 ubiquitin-protein ligase SMURF2-like [KO:K04678] [EC:2.3.2.26]
101286385  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
101289888  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X5 [KO:K04678] [EC:2.3.2.26]
101282406  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
101287684  ZFYVE16; zinc finger FYVE domain-containing protein 16 isoform X2 [KO:K04679]
101287254  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
101289349  RING-box protein 1-like [KO:K03868] [EC:2.3.2.32]
101280362  CUL1; cullin-1 [KO:K03347]
101276725  cullin-1-like [KO:K03347]
101289355  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
101273287  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
101289394  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101273830  RHOA; transforming protein RhoA [KO:K04513]
101278979  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
101274740  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101275690  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
101289109  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
101286814  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
101282700  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101286642  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X2 [KO:K04688] [EC:2.7.11.1]
101283084  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101287195  HAMP; hepcidin [KO:K23106]
101287558  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
101274357  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
101287106  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
101269887  ID4; DNA-binding protein inhibitor ID-4 isoform X2 [KO:K17695]
101273632  RBL1; retinoblastoma-like protein 1 isoform X2 [KO:K04681]
101290149  E2F5; transcription factor E2F5 isoform X2 [KO:K04682]
101270569  E2F4; transcription factor E2F4 isoform X2 [KO:K04682]
101275936  TFDP1; transcription factor Dp-1 isoform X2 [KO:K04683]
101281894  CREBBP; CREB-binding protein isoform X2 [KO:K04498] [EC:2.3.1.48]
101287751  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101284508  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
101287386  SKIL; ski-like protein isoform X1 [KO:K18499]
101283501  SKI; ski oncogene [KO:K26503]
101269812  SIN3A; paired amphipathic helix protein Sin3a isoform X1 [KO:K11644]
101277640  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
101271170  HDAC1; histone deacetylase 1 isoform X2 [KO:K06067] [EC:3.5.1.98]
101286776  LOW QUALITY PROTEIN: histone deacetylase 2-like [KO:K06067] [EC:3.5.1.98]
101286859  NCOR1; nuclear receptor corepressor 1 isoform X12 [KO:K04650]
101269398  TGIF1; homeobox protein TGIF1 isoform X3 [KO:K19383]
105747707  TGIF2; homeobox protein TGIF2 [KO:K19553]
101274490  MYC; myc proto-oncogene protein [KO:K04377]
105748701  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
101276528  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101280830  PITX2; pituitary homeobox 2 [KO:K04686]
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
Related
pathway
oor04010  MAPK signaling pathway
oor04110  Cell cycle
oor04120  Ubiquitin mediated proteolysis
oor04210  Apoptosis
KO pathway
ko04350   
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