KEGG   PATHWAY: chx04350
Entry
chx04350                    Pathway                                
Name
TGF-beta signaling pathway - Capra hircus (goat)
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
chx04350  TGF-beta signaling pathway
chx04350

Other DBs
GO: 0007179
Organism
Capra hircus (goat) [GN:chx]
Gene
100860789  BMP4; bone morphogenetic protein 4 precursor [KO:K04662]
100860793  BMP6; bone morphogenetic protein 6 isoform X1 [KO:K16620]
100860815  IFNG; interferon gamma precursor [KO:K04687]
100860831  BMP2; bone morphogenetic protein 2 precursor [KO:K21283]
100860911  SP1; transcription factor Sp1 [KO:K04684]
100860914  FST; follistatin precursor [KO:K04661]
100860918  ACVR2A; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
100860926  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
100860944  DCN; decorin precursor [KO:K04660]
100860960  INHBA; inhibin beta A chain precursor [KO:K04667]
100860969  GREM1; gremlin-1 [KO:K23318]
100860971  THBS1; thrombospondin-1 isoform X1 [KO:K16857]
100861019  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
100861211  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
100861228  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
100861232  TNF; tumor necrosis factor [KO:K03156]
100861241  BMPR1A; bone morphogenetic protein receptor type-1A precursor [KO:K04673] [EC:2.7.11.30]
100861250  INHBB; inhibin beta B chain [KO:K22687]
100861297  RPS6KB1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
100861300  TGFBR2; LOW QUALITY PROTEIN: TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
102168874  [KO:K19558]
102169293  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
102169319  [KO:K04688] [EC:2.7.11.1]
102169389  SMAD6; mothers against decapentaplegic homolog 6 isoform X1 [KO:K04677]
102169777  GDF6; growth/differentiation factor 6 [KO:K20012]
102170070  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
102170202  NODAL; nodal homolog [KO:K04666]
102170381  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
102170629  HAMP; hepcidin [KO:K23106]
102171022  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
102171262  MYC; myc proto-oncogene protein [KO:K04377]
102172197  TFRC; transferrin receptor protein 1 isoform X1 [KO:K06503]
102172205  [KO:K14736]
102172488  [KO:K14736]
102172733  GDF5; growth/differentiation factor 5 [KO:K04664]
102172824  E2F5; transcription factor E2F5 isoform X2 [KO:K04682]
102172895  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
102173240  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
102173331  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
102173944  BMP8B; bone morphogenetic protein 8B [KO:K16622]
102174738  [KO:K03094]
102174882  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
102175016  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102175214  NEO1; neogenin isoform X1 [KO:K06766]
102175489  SMAD9; mothers against decapentaplegic homolog 9 [KO:K16791]
102175649  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
102175820  TGIF1; homeobox protein TGIF1 isoform X1 [KO:K19383]
102175990  NRROS; negative regulator of reactive oxygen species [KO:K26317]
102176101  INHBE; inhibin beta E chain [KO:K22689]
102176275  ACVR2B; activin receptor type-2B precursor [KO:K13596] [EC:2.7.11.30]
102176324  RGMB; RGM domain family member B [KO:K06847]
102176397  INHBC; inhibin beta C chain [KO:K22688]
102176609  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
102176620  TFDP1; transcription factor Dp-1 [KO:K04683]
102176637  EMP3; epithelial membrane protein 3 [KO:K26257]
102176712  LRRC32; leucine-rich repeat-containing protein 32 [KO:K26316]
102176988  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
102177085  E2F4; transcription factor E2F4 isoform X2 [KO:K04682]
102177165  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
102177903  BMP7; bone morphogenetic protein 7 [KO:K16621]
102178016  SKIL; ski-like protein isoform X1 [KO:K18499]
102178640  TGIF2; homeobox protein TGIF2 isoform X1 [KO:K19553]
102179111  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
102180397  FBN1; fibrillin-1 [KO:K06825]
102180665  AMH; muellerian-inhibiting factor isoform X1 [KO:K04665]
102180667  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
102180740  PITX2; pituitary homeobox 2 [KO:K04686]
102181169  RHOA; transforming protein RhoA [KO:K04513]
102181349  HFE; hereditary hemochromatosis protein [KO:K26535]
102181631  CHRD; chordin isoform X1 [KO:K04657]
102182013  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102182533  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
102182675  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
102182747  HFE2; hemojuvelin isoform X1 [KO:K23100]
102182889  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
102183277  BMP5; bone morphogenetic protein 5 [KO:K04663]
102183441  [KO:K04668]
102183457  RGMA; repulsive guidance molecule A [KO:K23096]
102183621  FMOD; fibromodulin [KO:K08121]
102183633  NOG; noggin [KO:K04658]
102183990  [KO:K04668]
102185881  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
102186040  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102186139  SKI; ski oncogene [KO:K26503]
102186186  ACVR1B; activin receptor type-1B isoform X2 [KO:K13567] [EC:2.7.11.30]
102186939  IGSF1; immunoglobulin superfamily member 1 [KO:K26168]
102187112  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
102187369  BMP8A; bone morphogenetic protein 8A [KO:K16622]
102187383  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
102187544  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
102187566  LEMD3; inner nuclear membrane protein Man1 [KO:K19410]
102187642  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
102187767  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
102187824  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
102188080  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
102188136  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
102188455  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
102188771  [KO:K03868] [EC:2.3.2.32]
102188824  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102189002  TFR2; transferrin receptor protein 2 isoform X1 [KO:K23910]
102189270  TMEM53; transmembrane protein 53 [KO:K28359]
102189276  CUL1; cullin-1 [KO:K03347]
102189873  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
102189962  TGFB3; transforming growth factor beta-3 [KO:K13377]
102190008  SMAD7; mothers against decapentaplegic homolog 7 isoform X2 [KO:K19631]
102190077  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
102190794  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
102191347  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
102191364  TGFB1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
108633185  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
108633532  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
108637113  GDF7; growth/differentiation factor 7 [KO:K20013]
108637886  [KO:K04382] [EC:3.1.3.16]
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
chx04010  MAPK signaling pathway
chx04110  Cell cycle
chx04120  Ubiquitin mediated proteolysis
chx04210  Apoptosis
KO pathway
ko04350   

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