KEGG   PATHWAY: mjv04350
Entry
mjv04350                    Pathway                                
Name
TGF-beta signaling pathway - Manis javanica (Malayan pangolin)
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
mjv04350  TGF-beta signaling pathway
mjv04350

Other DBs
GO: 0007179
Organism
Manis javanica (Malayan pangolin) [GN:mjv]
Gene
108395277  CHRD; chordin isoform X3 [KO:K04657]
108393867  NOG; noggin [KO:K04658]
108406040  NBL1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
108394378  GREM1; gremlin-1 isoform X2 [KO:K23318]
108395153  GREM2; gremlin-2 isoform X1 [KO:K23318]
108400147  THBS1; thrombospondin-1 [KO:K16857]
108391667  DCN; decorin [KO:K04660]
108409925  FMOD; fibromodulin [KO:K08121]
108402589  left-right determination factor 1 [KO:K04668]
118970650  left-right determination factor 1-like [KO:K04668]
108393736  FST; follistatin isoform X1 [KO:K04661]
108403876  BMP2; bone morphogenetic protein 2 [KO:K21283]
108407678  BMP4; bone morphogenetic protein 4 isoform X2 [KO:K04662]
108391479  BMP6; bone morphogenetic protein 6 [KO:K16620]
108405634  INHBB; inhibin beta B chain [KO:K22687]
108405350  LOW QUALITY PROTEIN: serotransferrin [KO:K14736]
108394105  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
108390168  BMP7; bone morphogenetic protein 7 isoform X1 [KO:K16621]
108389334  LOW QUALITY PROTEIN: bone morphogenetic protein 8B-like [KO:K16622]
108386265  GDF5; growth/differentiation factor 5 [KO:K04664]
108395518  GDF6; growth/differentiation factor 6 [KO:K20012]
108401158  GDF7; growth/differentiation factor 7 [KO:K20013]
108384008  IFNG; interferon gamma [KO:K04687]
108397877  TNF; tumor necrosis factor [KO:K03156]
108403223  thrombospondin type-1 domain-containing protein 4 [KO:K23377]
108409610  FBN1; fibrillin-1 [KO:K06825]
108409270  LTBP1; latent-transforming growth factor beta-binding protein 1 [KO:K19559]
108383720  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
108403151  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
108404608  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
108408145  INHBA; inhibin beta A chain [KO:K04667]
108409973  INHBC; inhibin beta C chain [KO:K22688]
118966863  INHBE; inhibin beta E chain [KO:K22689]
108409338  NODAL; nodal homolog [KO:K04666]
108409236  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
108399139  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
108392510  ACVR1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
108409884  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
108391910  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
108400373  HJV; hemojuvelin isoform X1 [KO:K23100]
108395382  NEO1; neogenin isoform X1 [KO:K06766]
108400181  HFE; hereditary hemochromatosis protein isoform X4 [KO:K26535]
108409386  TFR2; transferrin receptor protein 2 isoform X4 [KO:K23910]
108383826  TFRC; transferrin receptor protein 1 isoform X1 [KO:K06503]
108402072  RGMA; repulsive guidance molecule A isoform X1 [KO:K23096]
108400264  RGMB; RGM domain family member B isoform X2 [KO:K06847]
108394781  AMHR2; anti-Muellerian hormone type-2 receptor isoform X1 [KO:K04672] [EC:2.7.11.30]
108394148  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
108391859  TGFBR2; TGF-beta receptor type-2 isoform X2 [KO:K04388] [EC:2.7.11.30]
108386779  EMP3; epithelial membrane protein 3 [KO:K26257]
108398546  LRRC32; transforming growth factor beta activator LRRC32 isoform X2 [KO:K26316]
108391172  NRROS; transforming growth factor beta activator LRRC33 isoform X1 [KO:K26317]
108398274  ACVR1B; activin receptor type-1B isoform X2 [KO:K13567] [EC:2.7.11.30]
108388382  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
108392567  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
108394872  immunoglobulin superfamily member 1 [KO:K26168]
108399312  BAMBI; BMP and activin membrane-bound inhibitor homolog isoform X1 [KO:K10162]
108385096  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
108410128  SMAD5; mothers against decapentaplegic homolog 5 isoform X2 [KO:K16790]
108390830  SMAD9; mothers against decapentaplegic homolog 9 [KO:K16791]
108400736  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
108404778  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
108394195  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
108389537  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
108399890  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
108403137  SMURF1; E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
108390219  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
108405576  ZFYVE16; LOW QUALITY PROTEIN: zinc finger FYVE domain-containing protein 16 [KO:K04679]
108395399  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
108394317  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
108386656  CUL1; cullin-1 [KO:K03347]
108406083  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
108398454  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
108400663  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108383250  transforming protein RhoA [KO:K04513]
108391302  ROCK1; rho-associated protein kinase 1 isoform X3 [KO:K04514] [EC:2.7.11.1]
108405702  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X2 [KO:K03456]
108405988  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
108406080  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
118972014  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
108393161  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
108401175  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
108398951  hepcidin [KO:K23106]
108394269  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
108384274  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
108388024  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
118967614  ID4; DNA-binding protein inhibitor ID-4 isoform X1 [KO:K17695]
108405977  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
108390313  E2F4; transcription factor E2F4 isoform X2 [KO:K04682]
108397991  transcription factor E2F4-like [KO:K04682]
108401870  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
108399968  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
108394315  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
108395362  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
108394782  SP1; transcription factor Sp1 [KO:K04684]
108393646  SKIL; LOW QUALITY PROTEIN: ski-like protein [KO:K18499]
108387013  SKI; ski oncogene [KO:K26503]
108392775  SIN3A; paired amphipathic helix protein Sin3a isoform X1 [KO:K11644]
108407680  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
108404446  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
108403991  NCOR1; nuclear receptor corepressor 1 isoform X13 [KO:K04650]
108395758  TGIF1; homeobox protein TGIF1 isoform X1 [KO:K19383]
108388031  TGIF2; homeobox protein TGIF2 isoform X1 [KO:K19553]
108399996  MYC; myc proto-oncogene protein [KO:K04377]
108386438  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
108407963  PITX2; pituitary homeobox 2 isoform X1 [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
mjv04010  MAPK signaling pathway
mjv04110  Cell cycle
mjv04120  Ubiquitin mediated proteolysis
mjv04210  Apoptosis
KO pathway
ko04350   
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