KEGG   PATHWAY: hai04350
Entry
hai04350                    Pathway                                
Name
TGF-beta signaling pathway - Hipposideros armiger (great roundleaf 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
hai04350  TGF-beta signaling pathway
hai04350

Other DBs
GO: 0007179
Organism
Hipposideros armiger (great roundleaf bat) [GN:hai]
Gene
109371368  CHRD; chordin isoform X1 [KO:K04657]
109371428  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
109371953  NODAL; nodal homolog isoform X1 [KO:K04666]
109372065  HAMP; hepcidin [KO:K23106]
109372307  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
109372345  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
109372591  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
109373073  TNF; tumor necrosis factor isoform X1 [KO:K03156]
109373347  INHBA; inhibin beta A chain [KO:K04667]
109373579  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
109373707  HFE2; hemojuvelin isoform X1 [KO:K23100]
109374676  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
109374904  TFR2; transferrin receptor protein 2 isoform X1 [KO:K23910]
109375038  GDF6; growth/differentiation factor 6 [KO:K20012]
109375765  HFE; hereditary hemochromatosis protein [KO:K26535]
109376080  BMP5; bone morphogenetic protein 5 [KO:K04663]
109376114  RHOA; transforming protein RhoA isoform X1 [KO:K04513]
109376590  TGFB1; transforming growth factor beta-1 [KO:K13375]
109376647  [KO:K14736]
109376789  DCN; decorin [KO:K04660]
109377484  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
109378414  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
109379244  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
109379450  PITX2; pituitary homeobox 2 [KO:K04686]
109379748  NOG; noggin [KO:K04658]
109379764  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
109379832  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
109379868  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
109380028  BMP7; bone morphogenetic protein 7 [KO:K16621]
109380319  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
109380392  RGMA; repulsive guidance molecule A [KO:K23096]
109381205  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
109381619  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
109381622  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
109381671  IFNG; interferon gamma [KO:K04687]
109381701  LEMD3; inner nuclear membrane protein Man1 [KO:K19410]
109382113  FST; follistatin isoform X1 [KO:K04661]
109382177  [KO:K04650]
109382554  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
109382613  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
109382627  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
109382969  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
109383211  MYC; myc proto-oncogene protein [KO:K04377]
109383383  TMEM53; transmembrane protein 53 [KO:K28359]
109383477  SKIL; ski-like protein [KO:K18499]
109383815  BMP2; bone morphogenetic protein 2 isoform X1 [KO:K21283]
109383949  TFDP1; transcription factor Dp-1 [KO:K04683]
109384080  THBS1; thrombospondin-1 [KO:K16857]
109384219  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
109384420  BMP4; bone morphogenetic protein 4 [KO:K04662]
109384459  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
109384760  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
109385242  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
109385268  SMAD6; mothers against decapentaplegic homolog 6 isoform X1 [KO:K04677]
109385323  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
109385343  GREM2; gremlin-2 [KO:K23318]
109385803  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
109386231  GREM1; gremlin-1 [KO:K23318]
109386292  LRRC32; leucine-rich repeat-containing protein 32 [KO:K26316]
109386421  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
109386448  FMOD; fibromodulin [KO:K08121]
109386715  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
109386975  NRROS; negative regulator of reactive oxygen species [KO:K26317]
109387574  E2F5; transcription factor E2F5 [KO:K04682]
109387796  TFRC; transferrin receptor protein 1 [KO:K06503]
109388212  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
109388225  SMAD7; mothers against decapentaplegic homolog 7 [KO:K19631]
109388474  SMAD9; mothers against decapentaplegic homolog 9 [KO:K16791]
109388695  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
109388785  LTBP1; latent-transforming growth factor beta-binding protein 1 [KO:K19559]
109388840  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
109388860  IGSF1; immunoglobulin superfamily member 1 [KO:K26168]
109388998  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
109389112  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
109389222  [KO:K14736]
109389553  RBL1; retinoblastoma-like protein 1 [KO:K04681]
109389564  GDF5; growth/differentiation factor 5 [KO:K04664]
109389608  TGIF2; homeobox protein TGIF2 [KO:K19553]
109389780  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
109390037  E2F4; transcription factor E2F4 [KO:K04682]
109390616  AMH; muellerian-inhibiting factor [KO:K04665]
109390735  INHBC; inhibin beta C chain [KO:K22688]
109390736  INHBE; inhibin beta E chain [KO:K22689]
109390927  [KO:K16622]
109391056  EMP3; epithelial membrane protein 3 [KO:K26257]
109391164  SKI; ski oncogene [KO:K26503]
109391669  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
109391759  NEO1; neogenin isoform X1 [KO:K06766]
109391772  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
109391846  SP1; transcription factor Sp1 [KO:K04684]
109391847  AMHR2; anti-Muellerian hormone type-2 receptor isoform X1 [KO:K04672] [EC:2.7.11.30]
109392135  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
109392203  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
109392262  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
109392275  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
109392962  GDF7; growth/differentiation factor 7 [KO:K20013]
109393116  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
109393492  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
109394441  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
109394466  [KO:K06825]
109394724  TGIF1; homeobox protein TGIF1 isoform X1 [KO:K19383]
109394900  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109395450  CUL1; cullin-1 isoform X1 [KO:K03347]
109395506  BMP6; bone morphogenetic protein 6 [KO:K16620]
109395581  NBL1; neuroblastoma suppressor of tumorigenicity 1 isoform X1 [KO:K19558]
109396680  INHBB; inhibin beta B chain [KO:K22687]
109396705  RGMB; RGM domain family member B isoform X1 [KO:K06847]
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
hai04010  MAPK signaling pathway
hai04110  Cell cycle
hai04120  Ubiquitin mediated proteolysis
hai04210  Apoptosis
KO pathway
ko04350   

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