KEGG   PATHWAY: pcad04350
Entry
pcad04350                   Pathway                                
Name
TGF-beta signaling pathway - Physeter macrocephalus (sperm whale)
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
pcad04350  TGF-beta signaling pathway
pcad04350

Other DBs
GO: 0007179
Organism
Physeter macrocephalus (sperm whale) [GN:pcad]
Gene
102973166  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
102973501  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
102973572  [KO:K19559]
102973758  FMOD; fibromodulin [KO:K08121]
102974160  GDF5; growth/differentiation factor 5 [KO:K04664]
102974448  SIN3A; paired amphipathic helix protein Sin3a isoform X1 [KO:K11644]
102974780  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
102974912  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102975052  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
102975571  NEO1; neogenin isoform X1 [KO:K06766]
102975643  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
102975928  INHBA; inhibin beta A chain [KO:K04667]
102976046  TFR2; transferrin receptor protein 2 [KO:K23910]
102976118  ACVR2A; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
102976367  [KO:K14736]
102976387  DCN; decorin [KO:K04660]
102976885  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
102977298  CHRD; chordin isoform X6 [KO:K04657]
102977345  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
102977782  [KO:K19558]
102978015  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
102978050  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
102978631  BMP2; bone morphogenetic protein 2 [KO:K21283]
102978826  INHBC; inhibin beta C chain [KO:K22688]
102979111  INHBE; inhibin beta E chain [KO:K22689]
102979506  GDF6; growth/differentiation factor 6 [KO:K20012]
102979656  [KO:K04685]
102979972  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
102980382  HJV; hemojuvelin isoform X1 [KO:K23100]
102980440  [KO:K03094]
102981211  ACVR1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
102981535  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
102981551  IFNG; interferon gamma [KO:K04687]
102982239  RGMB; repulsive guidance molecule B [KO:K06847]
102982384  [KO:K03094]
102982544  SKIL; ski-like protein [KO:K18499]
102982702  [KO:K03094]
102983069  TNF; tumor necrosis factor [KO:K03156]
102983370  [KO:K03094]
102983478  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
102983513  LRRC32; transforming growth factor beta activator LRRC32 isoform X1 [KO:K26316]
102983639  RHOA; transforming protein RhoA [KO:K04513]
102983663  BMPR1B; bone morphogenetic protein receptor type-1B isoform X2 [KO:K13578] [EC:2.7.11.30]
102984173  [KO:K03347]
102984265  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
102984305  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102985306  TGIF2; homeobox protein TGIF2 [KO:K19553]
102985437  TFRC; transferrin receptor protein 1 isoform X1 [KO:K06503]
102985506  NBL1; neuroblastoma suppressor of tumorigenicity 1 isoform X2 [KO:K19558]
102985694  IGSF1; immunoglobulin superfamily member 1 [KO:K26168]
102985903  [KO:K04658]
102986029  NODAL; nodal homolog [KO:K04666]
102986092  NRROS; transforming growth factor beta activator LRRC33 [KO:K26317]
102986517  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
102986645  [KO:K04668]
102986648  BAMBI; BMP and activin membrane-bound inhibitor homolog isoform X1 [KO:K10162]
102986914  NCOR1; nuclear receptor corepressor 1 [KO:K04650]
102986934  [KO:K04668]
102986988  [KO:K04682]
102987332  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
102987412  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
102988006  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
102988128  MYC; myc proto-oncogene protein [KO:K04377]
102988231  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
102988298  BMP6; bone morphogenetic protein 6 [KO:K16620]
102988410  E2F4; transcription factor E2F4 isoform X2 [KO:K04682]
102988416  GDF7; growth/differentiation factor 7 [KO:K20013]
102988463  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
102988528  ZFYVE16; zinc finger FYVE domain-containing protein 16 isoform X2 [KO:K04679]
102988603  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
102989074  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102989819  SMAD3; mothers against decapentaplegic homolog 3 isoform X2 [KO:K23605]
102989901  [KO:K03868] [EC:2.3.2.32]
102990094  ZFYVE9; LOW QUALITY PROTEIN: zinc finger FYVE domain-containing protein 9 [KO:K04679]
102990374  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
102990399  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
102990551  SKI; ski oncogene [KO:K26503]
102990826  FBN1; fibrillin-1 [KO:K06825]
102991111  EMP3; epithelial membrane protein 3 [KO:K26257]
102991182  HAMP; hepcidin [KO:K23106]
102991296  [KO:K14736]
102991331  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
102991367  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
102991425  [KO:K16622]
102991507  ACVR2B; activin receptor type-2B isoform X3 [KO:K13596] [EC:2.7.11.30]
102991594  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
102991643  ACVR1C; activin receptor type-1C isoform X2 [KO:K13568] [EC:2.7.11.30]
102991911  RBL1; retinoblastoma-like protein 1 isoform X4 [KO:K04681]
102992184  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X2 [KO:K03456]
102992588  SMAD5; mothers against decapentaplegic homolog 5 isoform X3 [KO:K16790]
102992659  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
102992728  GREM1; gremlin-1 [KO:K23318]
102992980  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
102993033  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
102993052  RGMA; repulsive guidance molecule A isoform X1 [KO:K23096]
102993283  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
102993328  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
102993732  CUL1; LOW QUALITY PROTEIN: cullin-1 [KO:K03347]
102993796  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102993806  HDAC2; histone deacetylase 2 isoform X3 [KO:K06067] [EC:3.5.1.98]
102993958  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
102994317  TGIF1; homeobox protein TGIF1 [KO:K19383]
102994393  FST; follistatin isoform X1 [KO:K04661]
102995420  THBS1; thrombospondin-1 [KO:K16857]
102995467  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
102995501  BMP7; bone morphogenetic protein 7 isoform X2 [KO:K16621]
102995806  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
102995949  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
102996539  AMHR2; anti-Muellerian hormone type-2 receptor isoform X6 [KO:K04672] [EC:2.7.11.30]
102996644  AMH; muellerian-inhibiting factor [KO:K04665]
112062207  [KO:K03347]
112062510  INHBB; inhibin beta B chain [KO:K22687]
112064360  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
112064697  [KO:K03868] [EC:2.3.2.32]
112065317  [KO:K16622]
112065991  NOG; noggin [KO:K04658]
114485354  [KO:K04498] [EC:2.3.1.48]
114486512  [KO:K13567] [EC:2.7.11.30]
129391324  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
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
pcad04010  MAPK signaling pathway
pcad04110  Cell cycle
pcad04120  Ubiquitin mediated proteolysis
pcad04210  Apoptosis
KO pathway
ko04350   

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