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Identification
HMDB Protein ID HMDBP14497
Secondary Accession Numbers None
Name Transforming growth factor beta-2 proprotein
Synonyms
  1. Cetermin
  2. Glioblastoma-derived T-cell suppressor factor
  3. G-TSF
Gene Name TGFB2
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Transforming growth factor beta-2 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively.Required to maintain the Transforming growth factor beta-2 (TGF-beta-2) chain in a latent state during storage in extracellular matrix (By similarity). Associates non-covalently with TGF-beta-2 and regulates its activation via interaction with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-2 (By similarity).Transforming growth factor beta-2: Multifunctional protein that regulates various processes such as angiogenesis and heart development (PubMed:22772371, PubMed:22772368). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains remain non-covalently linked rendering TGF-beta-2 inactive during storage in extracellular matrix (By similarity). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-2 and maintain it in a latent state during storage in extracellular milieus (By similarity). Once activated following release of LAP, TGF-beta-2 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity).
Pathways
  • AGE-RAGE signaling pathway in diabetic complications
  • Amoebiasis
  • Cell cycle
  • Cellular senescence
  • Chagas disease
  • Chronic myeloid leukemia
  • Colorectal cancer
  • Cytokine-cytokine receptor interaction
  • Diabetic cardiomyopathy
  • Dilated cardiomyopathy
  • FoxO signaling pathway
  • Gastric cancer
  • Hepatitis B
  • Hepatocellular carcinoma
  • Hippo signaling pathway
  • Human T-cell leukemia virus 1 infection
  • Hypertrophic cardiomyopathy
  • Inflammatory bowel disease
  • Leishmaniasis
  • Malaria
  • MAPK signaling pathway
  • MicroRNAs in cancer
  • Osteoclast differentiation
  • Pancreatic cancer
  • Proteoglycans in cancer
  • Renal cell carcinoma
  • Rheumatoid arthritis
  • TGF-beta signaling pathway
  • Toxoplasmosis
  • Tuberculosis
Reactions Not Available
GO Classification
Biological Process
cell-cell junction organization
ventricular septum morphogenesis
positive regulation of cell cycle
wound healing
neuron development
regulation of cell proliferation
odontogenesis
uterine wall breakdown
platelet degranulation
response to progesterone stimulus
cell cycle arrest
somatic stem cell division
positive regulation of cell proliferation
positive regulation of epithelial cell migration
dopamine biosynthetic process
cell migration
negative regulation of epithelial cell proliferation
SMAD protein signal transduction
positive regulation of protein secretion
response to wounding
BMP signaling pathway
positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation
response to drug
ventricular trabecula myocardium morphogenesis
embryo development ending in birth or egg hatching
positive regulation of pathway-restricted SMAD protein phosphorylation
ascending aorta morphogenesis
positive regulation of epithelial to mesenchymal transition
atrial septum morphogenesis
atrioventricular valve morphogenesis
cardiac muscle cell proliferation
cardiac right ventricle morphogenesis
cranial skeletal system development
embryonic limb morphogenesis
endocardial cushion fusion
endocardial cushion morphogenesis
positive regulation of heart contraction
heart valve morphogenesis
negative regulation of alkaline phosphatase activity
heart development
negative regulation of epithelial to mesenchymal transition involved in endocardial cushion formation
hemopoiesis
epithelial to mesenchymal transition
pharyngeal arch artery morphogenesis
positive regulation of cardioblast differentiation
positive regulation of cell adhesion mediated by integrin
neutrophil chemotaxis
positive regulation of integrin biosynthetic process
cell morphogenesis
positive regulation of immune response
positive regulation of ossification
positive regulation of pri-miRNA transcription by RNA polymerase II
positive regulation of timing of catagen
pulmonary valve morphogenesis
salivary gland morphogenesis
regulation of apoptotic process involved in outflow tract morphogenesis
regulation of timing of catagen
substantia propria of cornea development
skeletal system development
neural retina development
glial cell migration
eye development
positive regulation of cell growth
male gonad development
negative regulation of angiogenesis
negative regulation of cell growth
protein phosphorylation
positive regulation of Notch signaling pathway
inner ear development
collagen fibril organization
outflow tract septum morphogenesis
hair follicle morphogenesis
negative regulation of Ras protein signal transduction
regulation of transforming growth factor beta2 production
embryonic digestive tract development
heart morphogenesis
secondary palate development
activation of protein kinase activity
kidney development
transforming growth factor beta receptor signaling pathway
uterus development
negative regulation of cell proliferation
generation of neurons
positive regulation of stress-activated MAPK cascade
positive regulation of cell division
positive regulation of phosphatidylinositol 3-kinase cascade
neural tube closure
cardiac epithelial to mesenchymal transition
cardioblast differentiation
negative regulation of macrophage cytokine production
response to hypoxia
negative regulation of gene expression
positive regulation of neuron apoptotic process
extrinsic apoptotic signaling pathway
pathway-restricted SMAD protein phosphorylation
atrial septum primum morphogenesis
membranous septum morphogenesis
hair follicle development
cell death
Cellular Component
platelet alpha granule lumen
extracellular region
collagen-containing extracellular matrix
neuronal cell body
extracellular space
axon
Molecular Function
growth factor activity
beta-amyloid binding
receptor binding
protein homodimerization activity
type II transforming growth factor beta receptor binding
type III transforming growth factor beta receptor binding
cytokine activity
transforming growth factor beta receptor binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 414
Molecular Weight 47747.275
Theoretical pI 8.523
Pfam Domain Function
Signals
  • 1-20;
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P61812
UniProtKB/Swiss-Prot Entry Name TGFB2_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. David D, Cardoso J, Marques B, Marques R, Silva ED, Santos H, Boavida MG: Molecular characterization of a familial translocation implicates disruption of HDAC9 and possible position effect on TGFbeta2 in the pathogenesis of Peters' anomaly. Genomics. 2003 May;81(5):489-503. [PubMed:12706107 ]
  4. de Martin R, Haendler B, Hofer-Warbinek R, Gaugitsch H, Wrann M, Schlusener H, Seifert JM, Bodmer S, Fontana A, Hofer E: Complementary DNA for human glioblastoma-derived T cell suppressor factor, a novel member of the transforming growth factor-beta gene family. EMBO J. 1987 Dec 1;6(12):3673-7. [PubMed:3322813 ]
  5. Madisen L, Webb NR, Rose TM, Marquardt H, Ikeda T, Twardzik D, Seyedin S, Purchio AF: Transforming growth factor-beta 2: cDNA cloning and sequence analysis. DNA. 1988 Jan-Feb;7(1):1-8. [PubMed:3162414 ]
  6. Webb NR, Madisen L, Rose TM, Purchio AF: Structural and sequence analysis of TGF-beta 2 cDNA clones predicts two different precursor proteins produced by alternative mRNA splicing. DNA. 1988 Sep;7(7):493-7. [PubMed:2850146 ]
  7. Noma T, Glick AB, Geiser AG, O'Reilly MA, Miller J, Roberts AB, Sporn MB: Molecular cloning and structure of the human transforming growth factor-beta 2 gene promoter. Growth Factors. 1991;4(4):247-55. [PubMed:1764261 ]
  8. Marquardt H, Lioubin MN, Ikeda T: Complete amino acid sequence of human transforming growth factor type beta 2. J Biol Chem. 1987 Sep 5;262(25):12127-31. [PubMed:3476488 ]
  9. Nakajima M, Kizawa H, Saitoh M, Kou I, Miyazono K, Ikegawa S: Mechanisms for asporin function and regulation in articular cartilage. J Biol Chem. 2007 Nov 2;282(44):32185-92. Epub 2007 Sep 7. [PubMed:17827158 ]
  10. Daopin S, Piez KA, Ogawa Y, Davies DR: Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily. Science. 1992 Jul 17;257(5068):369-73. [PubMed:1631557 ]
  11. Schlunegger MP, Grutter MG: An unusual feature revealed by the crystal structure at 2.2 A resolution of human transforming growth factor-beta 2. Nature. 1992 Jul 30;358(6385):430-4. [PubMed:1641027 ]
  12. Alansari A, Hajeer AH, Bayat A, Eyre S, Carthy D, Ollier WE: Two novel polymorphisms in the human transforming growth factor beta 2 gene. Genes Immun. 2001 Aug;2(5):295-6. [PubMed:11528528 ]
  13. Tran DQ, Andersson J, Wang R, Ramsey H, Unutmaz D, Shevach EM: GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells. Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13445-50. doi: 10.1073/pnas.0901944106. Epub 2009 Jul 27. [PubMed:19651619 ]
  14. Boileau C, Guo DC, Hanna N, Regalado ES, Detaint D, Gong L, Varret M, Prakash SK, Li AH, d'Indy H, Braverman AC, Grandchamp B, Kwartler CS, Gouya L, Santos-Cortez RL, Abifadel M, Leal SM, Muti C, Shendure J, Gross MS, Rieder MJ, Vahanian A, Nickerson DA, Michel JB, Jondeau G, Milewicz DM: TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome. Nat Genet. 2012 Jul 8;44(8):916-21. doi: 10.1038/ng.2348. [PubMed:22772371 ]
  15. Lindsay ME, Schepers D, Bolar NA, Doyle JJ, Gallo E, Fert-Bober J, Kempers MJ, Fishman EK, Chen Y, Myers L, Bjeda D, Oswald G, Elias AF, Levy HP, Anderlid BM, Yang MH, Bongers EM, Timmermans J, Braverman AC, Canham N, Mortier GR, Brunner HG, Byers PH, Van Eyk J, Van Laer L, Dietz HC, Loeys BL: Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. Nat Genet. 2012 Jul 8;44(8):922-7. doi: 10.1038/ng.2349. [PubMed:22772368 ]
  16. Gago-Diaz M, Blanco-Verea A, Teixido-Tura G, Valenzuela I, Del Campo M, Borregan M, Sobrino B, Amigo J, Garcia-Dorado D, Evangelista A, Carracedo A, Brion M: Whole exome sequencing for the identification of a new mutation in TGFB2 involved in a familial case of non-syndromic aortic disease. Clin Chim Acta. 2014 Nov 1;437:88-92. doi: 10.1016/j.cca.2014.07.016. Epub 2014 Jul 19. [PubMed:25046559 ]