KEGG   PATHWAY: hcg04350
Entry
hcg04350                    Pathway                                
Name
TGF-beta signaling pathway - Hemicordylus capensis (graceful crag lizard)
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
hcg04350  TGF-beta signaling pathway
hcg04350

Other DBs
GO: 0007179
Organism
Hemicordylus capensis (graceful crag lizard) [GN:hcg]
Gene
128321931  TGIF1; homeobox protein TGIF1 isoform X1 [KO:K19383]
128321969  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
128322702  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
128322939  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
128323669  [KO:K04388] [EC:2.7.11.30]
128324239  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
128324346  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
128324500  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
128324521  GDF5; growth/differentiation factor 5 [KO:K04664]
128324890  BMP7; bone morphogenetic protein 7 [KO:K16621]
128325030  TGIF2; homeobox protein TGIF2 isoform X1 [KO:K19553]
128325218  GDF6; growth/differentiation factor 6 [KO:K20012]
128325780  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
128326717  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
128327088  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
128327102  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
128327127  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
128327301  DCN; decorin [KO:K04660]
128327334  IFNG; interferon gamma isoform X1 [KO:K04687]
128328019  THBS1; thrombospondin-1 isoform X1 [KO:K16857]
128329030  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
128329136  ACVR1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
128329154  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
128329227  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
128330043  [KO:K23100]
128330226  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
128330376  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
128330595  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
128330764  INHBA; inhibin beta A chain [KO:K04667]
128331704  EMP3; epithelial membrane protein 3 [KO:K26257]
128331827  CUL1; cullin-1 [KO:K03347]
128331900  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
128332006  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
128332172  TFR2; transferrin receptor protein 2 isoform X1 [KO:K23910]
128332607  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
128332663  HAMP; hepcidin [KO:K23106]
128332765  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
128333011  BMP8A; bone morphogenetic protein 8A [KO:K16622]
128333078  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
128333363  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
128333393  [KO:K04662]
128333880  [KO:K04666]
128334503  E2F4; transcription factor E2F4 [KO:K04682]
128334769  FBN1; fibrillin-1 isoform X1 [KO:K06825]
128334782  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
128334793  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
128334819  GREM1; gremlin-1 [KO:K23318]
128334860  NEO1; neogenin isoform X1 [KO:K06766]
128334986  SIN3A; paired amphipathic helix protein Sin3a isoform X1 [KO:K11644]
128335208  RGMA; repulsive guidance molecule A isoform X1 [KO:K23096]
128335215  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
128335561  [KO:K26316]
128335929  [KO:K04650]
128335990  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
128336184  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
128336314  [KO:K04658]
128336393  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
128336483  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
128336909  [KO:K13376]
128337022  [KO:K04501]
128337030  [KO:K04677]
128337154  [KO:K23100]
128337970  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
128338359  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
128338578  NBL1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
128338720  SKI; ski oncogene [KO:K26503]
128339230  BMP2; bone morphogenetic protein 2 [KO:K21283]
128339914  BMP4; bone morphogenetic protein 4 [KO:K04662]
128339949  BMP5; bone morphogenetic protein 5 [KO:K04663]
128340257  GDF7; growth/differentiation factor 7 [KO:K20013]
128340537  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
128340609  INHBB; inhibin beta B chain [KO:K22687]
128341130  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
128341842  FST; follistatin isoform X1 [KO:K04661]
128342403  NOG; noggin [KO:K04658]
128342787  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
128343216  AMH; muellerian-inhibiting factor [KO:K04665]
128343476  [KO:K23096]
128343525  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
128343654  [KO:K04685]
128343787  [KO:K21283]
128343931  ZFYVE16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
128344518  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
128344917  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
128345072  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
128345095  [KO:K23100]
128345307  RHOA; transforming protein RhoA [KO:K04513]
128345451  SMAD5; mothers against decapentaplegic homolog 5 isoform X1 [KO:K16790]
128345731  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
128345825  RGMB; repulsive guidance molecule B isoform X1 [KO:K06847]
128346024  [KO:K03156]
128346085  [KO:K22689]
128346623  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
128346740  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
128346925  [KO:K04513]
128346977  GREM2; gremlin-2 [KO:K23318]
128347677  AMHR2; anti-Muellerian hormone type-2 receptor isoform X1 [KO:K04672] [EC:2.7.11.30]
128348160  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
128348752  CHRD; chordin isoform X1 [KO:K04657]
128349065  NRROS; transforming growth factor beta activator LRRC33 isoform X1 [KO:K26317]
128349880  SKIL; ski-like protein isoform X1 [KO:K18499]
128349989  [KO:K04668]
128350238  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
128350566  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
128350792  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
128350885  TFRC; transferrin receptor protein 1 isoform X1 [KO:K06503]
128351212  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
128351495  TF; serotransferrin [KO:K14736]
128351506  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
128352433  NODAL; nodal homolog isoform X1 [KO:K04666]
128352845  BMP6; bone morphogenetic protein 6 [KO:K16620]
128352968  FMOD; fibromodulin isoform X1 [KO:K08121]
128353003  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
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
hcg04010  MAPK signaling pathway
hcg04110  Cell cycle
hcg04120  Ubiquitin mediated proteolysis
hcg04210  Apoptosis
KO pathway
ko04350   

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