KEGG   PATHWAY: mlx04350
Entry
mlx04350                    Pathway                                
Name
TGF-beta signaling pathway - Mirounga leonina (Southern elephant seal)
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
mlx04350  TGF-beta signaling pathway
mlx04350

Other DBs
GO: 0007179
Organism
Mirounga leonina (Southern elephant seal) [GN:mlx]
Gene
117997455  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
117997483  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
117998217  EMP3; epithelial membrane protein 3 [KO:K26257]
117998379  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
117998441  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
117998460  [KO:K16622]
117998639  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
117998640  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
117998900  DCN; decorin isoform X1 [KO:K04660]
117999361  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
117999424  TFR2; transferrin receptor protein 2 [KO:K23910]
117999637  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
117999826  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
118000110  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
118000273  HJV; hemojuvelin isoform X1 [KO:K23100]
118000550  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
118001462  BMP5; bone morphogenetic protein 5 [KO:K04663]
118001989  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
118002167  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
118002625  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
118002661  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
118003234  GREM1; gremlin-1 isoform X1 [KO:K23318]
118003393  NEO1; neogenin isoform X1 [KO:K06766]
118003430  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
118003485  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
118003603  FBN1; fibrillin-1 [KO:K06825]
118003683  SMAD6; mothers against decapentaplegic homolog 6 isoform X1 [KO:K04677]
118003718  THSD4; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
118003756  THBS1; thrombospondin-1 [KO:K16857]
118003865  [KO:K14736]
118003867  [KO:K14736]
118004063  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
118004426  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
118004433  TGIF1; homeobox protein TGIF1 [KO:K19383]
118004574  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
118004611  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
118004627  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
118005670  RHOA; transforming protein RhoA [KO:K04513]
118005687  AMH; muellerian-inhibiting factor isoform X1 [KO:K04665]
118006208  SKIL; ski-like protein [KO:K18499]
118006619  [KO:K04661]
118006749  [KO:K04661]
118006903  CHRD; chordin isoform X1 [KO:K04657]
118006975  NRROS; transforming growth factor beta activator LRRC33 isoform X1 [KO:K26317]
118006987  TFRC; transferrin receptor protein 1 isoform X1 [KO:K06503]
118007295  [KO:K17693]
118007353  [KO:K17693]
118007400  GDF7; growth/differentiation factor 7 [KO:K20013]
118007514  LTBP1; latent-transforming growth factor beta-binding protein 1 [KO:K19559]
118008418  IFNG; interferon gamma [KO:K04687]
118008427  INHBE; inhibin beta E chain [KO:K22689]
118008428  INHBC; inhibin beta C chain [KO:K22688]
118008614  LEMD3; inner nuclear membrane protein Man1 isoform X1 [KO:K19410]
118008791  AMHR2; LOW QUALITY PROTEIN: anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
118008792  SP1; transcription factor Sp1 [KO:K04684]
118008827  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
118009212  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
118009505  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
118009990  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
118010315  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
118011109  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
118011254  BMP2; bone morphogenetic protein 2 [KO:K21283]
118011420  GDF5; growth/differentiation factor 5 [KO:K04664]
118011443  TGIF2; homeobox protein TGIF2 [KO:K19553]
118011456  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
118011567  IGSF1; immunoglobulin superfamily member 1 [KO:K26168]
118012135  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
118012425  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
118012426  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
118012466  ACVR2A; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
118012553  INHBB; inhibin beta B chain [KO:K22687]
118012847  [KO:K04668]
118013012  [KO:K04668]
118013220  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
118014087  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
118014176  FMOD; fibromodulin [KO:K08121]
118014539  GREM2; gremlin-2 isoform X1 [KO:K23318]
118014755  GDF6; growth/differentiation factor 6 [KO:K20012]
118014975  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
118014995  [KO:K06067] [EC:3.5.1.98]
118015212  MYC; myc proto-oncogene protein [KO:K04377]
118016129  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
118016639  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
118016640  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
118016664  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
118016947  ZFYVE16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
118017041  RGMB; RGM domain family member B [KO:K06847]
118017899  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
118018063  [KO:K04685]
118018355  [KO:K04666]
118019094  [KO:K04666]
118019410  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
118019508  TMEM53; transmembrane protein 53 [KO:K28359]
118019746  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
118019894  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
118019934  NBL1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
118020094  SKI; ski oncogene isoform X1 [KO:K26503]
118021218  CUL1; cullin-1 [KO:K03347]
118021774  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
118022276  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
118022555  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
118022632  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
118022878  HAMP; hepcidin [KO:K23106]
118023019  RGMA; repulsive guidance molecule A isoform X1 [KO:K23096]
118023685  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
118023991  BMP7; bone morphogenetic protein 7 [KO:K16621]
118024363  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
118024549  INHBA; inhibin beta A chain [KO:K04667]
118024673  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
118025038  NOG; noggin [KO:K04658]
118027096  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
118027255  TNF; tumor necrosis factor [KO:K03156]
118027440  BMP6; bone morphogenetic protein 6 [KO:K16620]
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
mlx04010  MAPK signaling pathway
mlx04110  Cell cycle
mlx04120  Ubiquitin mediated proteolysis
mlx04210  Apoptosis
KO pathway
ko04350   

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