KEGG   PATHWAY: rfq04350
Entry
rfq04350                    Pathway                                
Name
TGF-beta signaling pathway - Rhinolophus ferrumequinum (greater horseshoe bat)
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
rfq04350  TGF-beta signaling pathway
rfq04350

Other DBs
GO: 0007179
Organism
Rhinolophus ferrumequinum (greater horseshoe bat) [GN:rfq]
Gene
117011743  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
117011752  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
117011769  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
117011826  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
117011996  TGIF1; homeobox protein TGIF1 [KO:K19383]
117012120  INHBA; inhibin beta A chain [KO:K04667]
117012731  NOG; noggin [KO:K04658]
117012984  NRROS; transforming growth factor beta activator LRRC33 [KO:K26317]
117013482  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
117013738  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
117013759  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
117013996  CHRD; chordin isoform X1 [KO:K04657]
117014254  FMOD; fibromodulin [KO:K08121]
117014695  HJV; hemojuvelin [KO:K23100]
117015163  [KO:K04674] [EC:2.7.11.30]
117015301  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
117015725  TGIF2; homeobox protein TGIF2 [KO:K19553]
117015990  GDF5; growth/differentiation factor 5 [KO:K04664]
117016157  BMP2; bone morphogenetic protein 2 [KO:K21283]
117016167  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
117016228  BMP7; bone morphogenetic protein 7 [KO:K16621]
117016339  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
117016687  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
117016717  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
117016737  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
117016937  [KO:K17693]
117017062  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
117017296  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117018094  CUL1; cullin-1 isoform X1 [KO:K03347]
117018527  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
117018602  GREM2; gremlin-2 [KO:K23318]
117018681  [KO:K04668]
117018682  [KO:K04668]
117018853  RGMA; repulsive guidance molecule A isoform X1 [KO:K23096]
117019455  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
117020338  TNF; tumor necrosis factor [KO:K03156]
117020431  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
117020658  [KO:K26168]
117020846  BMP5; bone morphogenetic protein 5 [KO:K04663]
117021335  TFDP1; transcription factor Dp-1 [KO:K04683]
117021536  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
117021745  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
117021939  PITX2; LOW QUALITY PROTEIN: pituitary homeobox 2 [KO:K04686]
117022451  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
117022555  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
117023034  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
117023079  NEO1; neogenin isoform X1 [KO:K06766]
117023095  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
117023341  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
117023483  FBN1; fibrillin-1 isoform X1 [KO:K06825]
117023582  THBS1; thrombospondin-1 [KO:K16857]
117023992  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
117024062  GREM1; gremlin-1 isoform X1 [KO:K23318]
117024157  BMP4; bone morphogenetic protein 4 [KO:K04662]
117024184  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
117024863  RGMB; RGM domain family member B [KO:K06847]
117025263  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
117025316  TFR2; transferrin receptor protein 2 [KO:K23910]
117025363  FST; follistatin isoform X1 [KO:K04661]
117025450  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
117025507  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
117025927  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
117025950  INHBB; inhibin beta B chain [KO:K22687]
117026159  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
117026518  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
117026604  TMEM53; transmembrane protein 53 isoform X1 [KO:K28359]
117026689  BMP8A; bone morphogenetic protein 8A isoform X1 [KO:K16622]
117026730  SKI; ski oncogene [KO:K26503]
117026825  BMP6; bone morphogenetic protein 6 [KO:K16620]
117026930  BMP8B; bone morphogenetic protein 8B [KO:K16622]
117026992  NBL1; neuroblastoma suppressor of tumorigenicity 1 isoform X1 [KO:K19558]
117027538  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
117027584  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
117027749  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
117028064  INHBC; inhibin beta C chain [KO:K22688]
117028097  INHBE; inhibin beta E chain [KO:K22689]
117028101  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
117028155  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
117028220  DCN; decorin [KO:K04660]
117028359  SP1; transcription factor Sp1 [KO:K04684]
117028582  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
117028995  LEMD3; inner nuclear membrane protein Man1 isoform X1 [KO:K19410]
117029081  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
117029185  IFNG; interferon gamma [KO:K04687]
117029822  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
117030068  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
117031075  LRRC32; transforming growth factor beta activator LRRC32 isoform X1 [KO:K26316]
117032140  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
117032431  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
117032961  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
117033197  GDF7; growth/differentiation factor 7 [KO:K20013]
117033448  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
117033503  TFRC; transferrin receptor protein 1 isoform X1 [KO:K06503]
117033940  GDF6; growth/differentiation factor 6 [KO:K20012]
117034006  E2F5; transcription factor E2F5 [KO:K04682]
117034063  MYC; myc proto-oncogene protein [KO:K04377]
117034454  [KO:K03094]
117034671  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
117034985  HAMP; hepcidin [KO:K23106]
117035087  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
117035153  EMP3; epithelial membrane protein 3 [KO:K26257]
117035231  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
117036084  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
117036135  [KO:K03094]
117036400  NODAL; nodal homolog [KO:K04666]
117036663  RHOA; transforming protein RhoA [KO:K04513]
117036921  TGFBR2; LOW QUALITY PROTEIN: TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
117037206  [KO:K14736]
117037207  [KO:K14736]
117037311  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
117037869  AMH; muellerian-inhibiting factor [KO:K04665]
117038270  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
117038689  SKIL; 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
rfq04010  MAPK signaling pathway
rfq04110  Cell cycle
rfq04120  Ubiquitin mediated proteolysis
rfq04210  Apoptosis
KO pathway
ko04350   

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