KEGG   PATHWAY: oas04350
Entry
oas04350                    Pathway                                
Name
TGF-beta signaling pathway - Ovis aries (sheep)
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
oas04350  TGF-beta signaling pathway
oas04350

Other DBs
GO: 0007179
Organism
Ovis aries (sheep) [GN:oas]
Gene
443243  CHRD; chordin isoform X1 [KO:K04657]
780490  NOG; noggin precursor [KO:K04658]
101108197  NBL1; neuroblastoma suppressor of tumorigenicity 1 isoform X2 [KO:K19558]
101102396  GREM1; gremlin-1 isoform X1 [KO:K23318]
101106433  THBS1; thrombospondin-1 isoform X6 [KO:K16857]
443048  DCN; decorin precursor [KO:K04660]
101111037  FMOD; fibromodulin [KO:K08121]
101105347  left-right determination factor 2-like [KO:K04668]
101111566  left-right determination factor 2 [KO:K04668]
443323  FST; follistatin precursor [KO:K04661]
101117688  BMP2; bone morphogenetic protein 2 [KO:K21283]
443502  BMP4; bone morphogenetic protein 4 precursor [KO:K04662]
443174  BMP6; bone morphogenetic protein 6 isoform X1 [KO:K16620]
101119286  INHBB; inhibin beta B chain [KO:K22687]
443000  TF; LOW QUALITY PROTEIN: serotransferrin [KO:K14736]
101117129  inhibitor of carbonic anhydrase-like isoform X2 [KO:K14736]
101107231  BMP5; bone morphogenetic protein 5 [KO:K04663]
443175  BMP7; bone morphogenetic protein 7 precursor [KO:K16621]
105604271  BMP8B; bone morphogenetic protein 8B [KO:K16622]
101120626  bone morphogenetic protein 8B [KO:K16622]
101116499  GDF5; growth/differentiation factor 5 [KO:K04664]
101108925  GDF6; growth/differentiation factor 6 isoform X1 [KO:K20012]
106990980  GDF7; growth/differentiation factor 7 [KO:K20013]
101121773  AMH; muellerian-inhibiting factor precursor [KO:K04665]
443396  IFNG; interferon gamma precursor [KO:K04687]
443540  TNF; tumor necrosis factor [KO:K03156]
101115035  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X2 [KO:K23377]
101109620  FBN1; fibrillin-1 isoform X1 [KO:K06825]
101102219  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
443417  TGFB1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
554322  TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
554323  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
443524  INHBA; inhibin beta A chain precursor [KO:K04667]
101121843  INHBC; inhibin beta C chain [KO:K22688]
101121588  INHBE; inhibin beta E chain [KO:K22689]
101110384  NODAL; nodal homolog [KO:K04666]
101112282  BMPR1A; bone morphogenetic protein receptor type-1A precursor [KO:K04673] [EC:2.7.11.30]
443454  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
443161  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
101103793  BMPR2; bone morphogenetic protein receptor type-2 precursor [KO:K04671] [EC:2.7.11.30]
443304  ACVR2A; activin receptor type-2A precursor [KO:K04670] [EC:2.7.11.30]
101114997  HJV; hemojuvelin isoform X1 [KO:K23100]
101117081  NEO1; neogenin isoform X4 [KO:K06766]
101105539  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
101103367  TFR2; transferrin receptor protein 2 isoform X3 [KO:K23910]
100885768  TFRC; transferrin receptor protein 1 isoform X2 [KO:K06503]
101113702  RGMA; repulsive guidance molecule A isoform X1 [KO:K23096]
101111545  RGMB; repulsive guidance molecule B [KO:K06847]
101109693  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
554326  TGFBR1; TGF-beta receptor type-1 isoform X2 [KO:K04674] [EC:2.7.11.30]
494191  TGFBR2; TGF-beta receptor type-2 isoform X2 [KO:K04388] [EC:2.7.11.30]
101121114  EMP3; epithelial membrane protein 3 [KO:K26257]
101112256  LRRC32; transforming growth factor beta activator LRRC32 isoform X2 [KO:K26316]
101123000  NRROS; transforming growth factor beta activator LRRC33 isoform X2 [KO:K26317]
101113836  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
443156  ACVR2B; activin receptor type-2B isoform X2 [KO:K13596] [EC:2.7.11.30]
101111867  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
101111779  IGSF1; immunoglobulin superfamily member 1 isoform X1 [KO:K26168]
443242  BAMBI; BMP and activin membrane-bound inhibitor homolog precursor [KO:K10162]
443229  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
443172  SMAD5; mothers against decapentaplegic homolog 5 isoform X1 [KO:K16790]
101105084  SMAD9; mothers against decapentaplegic homolog 9 [KO:K16791]
101114231  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
443169  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
443171  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
101103068  SMAD6; mothers against decapentaplegic homolog 6 isoform X1 [KO:K04677]
101111414  SMAD7; mothers against decapentaplegic homolog 7 isoform X2 [KO:K19631]
101106698  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
101103370  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
101120662  ZFYVE16; zinc finger FYVE domain-containing protein 16 isoform X2 [KO:K04679]
101114400  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
101109871  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X2 [KO:K03868] [EC:2.3.2.32]
101106584  CUL1; cullin-1 [KO:K03347]
101115786  cullin-1-like [KO:K03347]
100240716  S-phase kinase-associated protein 1 [KO:K03094]
114108593  SKP1; S-phase kinase-associated protein 1 isoform X4 [KO:K03094]
114112940  S-phase kinase-associated protein 1-like [KO:K03094]
114113951  S-phase kinase-associated protein 1-like [KO:K03094]
101115485  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
101123008  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100302078  RHOA; transforming protein RhoA [KO:K04513]
114116812  transforming protein RhoA-like [KO:K04513]
101106246  transforming protein RhoA [KO:K04513]
101102442  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
101115302  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101108511  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X2 [KO:K03456]
101109519  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like [KO:K03456]
114111443  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like [KO:K03456]
101114930  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
443009  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
101108352  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
101107371  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101109574  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
100500730  HAMP; hepcidin precursor [KO:K23106]
101111650  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
101115522  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
100415775  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
101122061  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
114111168  DNA-binding protein inhibitor ID-4-like [KO:K17695]
101102328  RBL1; retinoblastoma-like protein 1 [KO:K04681]
101114117  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
101106963  E2F4; transcription factor E2F4 isoform X4 [KO:K04682]
114113619  LOW QUALITY PROTEIN: transcription factor E2F4-like [KO:K04682]
101117516  TFDP1; transcription factor Dp-1 [KO:K04683]
101110136  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
101123600  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
101104139  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
101117895  SKIL; ski-like protein isoform X2 [KO:K18499]
105609732  SKI; ski oncogene [KO:K26503]
101106112  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
100820752  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
101107708  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
101117774  NCOR1; nuclear receptor corepressor 1 isoform X10 [KO:K04650]
101105544  TGIF1; homeobox protein TGIF1 isoform X1 [KO:K19383]
101114141  homeobox protein TGIF1-like [KO:K19383]
105601861  TGIF2; homeobox protein TGIF2 [KO:K19553]
443447  MYC; myc proto-oncogene protein [KO:K04377]
101107164  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101116988  PITX2; pituitary homeobox 2 isoform X1 [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
oas04010  MAPK signaling pathway
oas04110  Cell cycle
oas04120  Ubiquitin mediated proteolysis
oas04210  Apoptosis
KO pathway
ko04350   
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