KEGG   PATHWAY: ecb04350
Entry
ecb04350                    Pathway                                
Name
TGF-beta signaling pathway - Equus caballus (horse)
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
ecb04350  TGF-beta signaling pathway
ecb04350

Other DBs
GO: 0007179
Organism
Equus caballus (horse) [GN:ecb]
Gene
100067164  CHRD; chordin isoform X1 [KO:K04657]
100033935  NOG; noggin [KO:K04658]
100071893  uncharacterized protein LOC100071893 [KO:K19558]
100057765  GREM1; gremlin-1 [KO:K23318]
100060243  GREM2; gremlin-2 [KO:K23318]
100057478  THBS1; thrombospondin-1 precursor [KO:K16857]
100034120  DCN; decorin precursor [KO:K04660]
100009678  FMOD; fibromodulin precursor [KO:K08121]
100147245  left-right determination factor 1 [KO:K04668]
100054366  left-right determination factor 1-like isoform X1 [KO:K04668]
100033825  FST; follistatin precursor [KO:K04661]
100051701  BMP2; bone morphogenetic protein 2 isoform X1 [KO:K21283]
100034048  BMP4; bone morphogenetic protein 4 precursor [KO:K04662]
100033934  BMP6; bone morphogenetic protein 6 [KO:K16620]
100067535  INHBB; inhibin beta B chain [KO:K22687]
100034176  TF; serotransferrin precursor [KO:K14736]
100146633  inhibitor of carbonic anhydrase [KO:K14736]
100056806  BMP5; bone morphogenetic protein 5 [KO:K04663]
100050299  BMP7; bone morphogenetic protein 7 precursor [KO:K16621]
102150286  BMP8B; bone morphogenetic protein 8B [KO:K16622]
100068680  bone morphogenetic protein 8B [KO:K16622]
100034228  GDF5; growth/differentiation factor 5 precursor [KO:K04664]
100059475  GDF6; growth/differentiation factor 6 [KO:K20012]
100147101  GDF7; growth/differentiation factor 7 [KO:K20013]
102148318  AMH; muellerian-inhibiting factor precursor [KO:K04665]
100034181  IFNG; interferon gamma precursor [KO:K04687]
100033834  TNF; tumor necrosis factor [KO:K03156]
100063949  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
100055741  FBN1; fibrillin-1 isoform X1 [KO:K06825]
100070522  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X9 [KO:K19559]
100033900  TGFB1; transforming growth factor beta-1 precursor [KO:K13375]
100050377  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
111771316  transforming growth factor beta-2-like isoform X1 [KO:K13376]
100051765  TGFB3; transforming growth factor beta-3 [KO:K13377]
100034076  INHBA; inhibin beta A chain precursor [KO:K04667]
100053175  INHBC; inhibin beta C chain [KO:K22688]
100050257  INHBE; inhibin beta E chain [KO:K22689]
100072735  NODAL; nodal homolog [KO:K04666]
100064367  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
100053554  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
100050899  ACVR1; activin receptor type-1 isoform X2 [KO:K04675] [EC:2.7.11.30]
100067195  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
100049823  ACVR2A; activin receptor type-2A precursor [KO:K04670] [EC:2.7.11.30]
111773537  HFE2; hemojuvelin isoform X1 [KO:K23100]
100063194  NEO1; neogenin isoform X1 [KO:K06766]
100053350  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
100067467  TFR2; transferrin receptor protein 2 [KO:K23910]
100034089  TFRC; transferrin receptor protein 1 [KO:K06503]
100051861  RGMA; repulsive guidance molecule A [KO:K23096]
100073220  RGMB; RGM domain family member B [KO:K06847]
100063905  AMHR2; anti-Muellerian hormone type-2 receptor isoform X1 [KO:K04672] [EC:2.7.11.30]
100034117  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
100033860  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
100050794  EMP3; epithelial membrane protein 3 [KO:K26257]
100063749  LRRC32; leucine-rich repeat-containing protein 32 [KO:K26316]
100069731  NRROS; negative regulator of reactive oxygen species [KO:K26317]
100062619  ACVR1B; activin receptor type-1B isoform X2 [KO:K13567] [EC:2.7.11.30]
100053588  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
100059573  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
100058129  IGSF1; immunoglobulin superfamily member 1 [KO:K26168]
100063997  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
100033850  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
100033851  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
100062493  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
100033843  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100033845  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100033846  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
100033852  SMAD6; mothers against decapentaplegic homolog 6 isoform X1 [KO:K04677]
100033853  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
100063241  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
100064082  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
100062152  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
100065363  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
100055581  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
100051217  CUL1; cullin-1 [KO:K03347]
100062946  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
100057701  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
100066173  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100053343  RHOA; transforming protein RhoA [KO:K04513]
100034056  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
100062627  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100070408  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
100062224  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100053005  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
100057481  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
100050728  HAMP; hepcidin precursor [KO:K23106]
100068419  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
100057240  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
100071592  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
100066589  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
100069786  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
100053119  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
100056139  E2F5; LOW QUALITY PROTEIN: transcription factor E2F5 [KO:K04682]
100069163  TFDP1; transcription factor Dp-1 [KO:K04683]
100055626  EP300; histone acetyltransferase p300 isoform X2 [KO:K04498] [EC:2.3.1.48]
100069613  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
100629527  SP1; transcription factor Sp1 [KO:K04684]
100057606  SKIL; ski-like protein [KO:K18499]
100033833  SKI; ski oncogene [KO:K26503]
100051174  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
100072578  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
100070281  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
100063285  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
100051444  TGIF1; homeobox protein TGIF1 isoform X2 [KO:K19383]
102149210  TGIF2; homeobox protein TGIF2 [KO:K19553]
100068097  MYC; myc proto-oncogene protein [KO:K04377]
100034122  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100146441  PITX2; pituitary homeobox 2 isoform X2 [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
ecb04010  MAPK signaling pathway
ecb04110  Cell cycle
ecb04120  Ubiquitin mediated proteolysis
ecb04210  Apoptosis
KO pathway
ko04350   
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