TGFBI (transforming growth factor, beta-induced, 68kDa)

2009-02-01   Chaoyu Ma , Xiao-Fan Wang 

Dept of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA

Identity

HGNC
LOCATION
5q31.1
LOCUSID
ALIAS
BIGH3,CDB1,CDG2,CDGG1,CSD,CSD1,CSD2,CSD3,EBMD,LCD1
FUSION GENES

DNA/RNA

Description

19 exons.

Transcription

2.8 Kb mRNA, 2049 bp open reading frame.

Proteins

Atlas Image
TGFBI contains a secretory signal peptide (SP) at the N-terminus, followed by a cysteine-rich domain (CRD), four internal homologous domains (FAS), and a C-terminal RGD motif.

Description

TGFBI is a 683 amino acid extracellular matrix protein, 68 kDa. Contains an N-terminal secretory signal peptide, a cysteine-rich domain, four internal homologous repeats (fasciclin-like FAS domains), and a C-terminal RGD motif.

Expression

TGFBI is normally found in thymus, bone marrow, spleen, brain, heart, skeleton muscle, lung, kidney, liver, pancreas, and prostate.

Localisation

TGFBI is an extracellular matrix protein. It localizes in the extracellular matrix.

Function

Binds to type I, II, IV, VI collagens and fibronectin. The RGD motif may serve as a ligand recognition sequence for integrins. The protein may be involved in cell-matrix interactions, cell adhesion, migration and differentiation. The protein may be involved in endochondrial bone formation in cartilage. The roles of TGFBI in malignant progression are controversial. Some studies suggested that TGFBI suppresses the progression of ovarian, lung cancer and neuroblastomas, while other reports identify TGFBI as an overexpressed gene in colon, pancreatic, and liver cancer.

Homology

TGFBI contains four FAS1 domains. Proteins cantaining the FAS domain include Arabidopsis fasciclin-like arabinogalactan proteins, bacterial immunogenic protein MPT70, human extracellular matrix protein periostin, and mammalian stabilin proteins.

Mutations

Germinal

Mutations in the human TGFBI gene have been linked to several inherited autosmal dominant corneal dystrophies. The abnormal protein deposits in the forms of amyloid fibrils and/or non-amyloid amorphous affregations in the corneal matrix. Progressive corneal cloudiness eventually leads to severe visual loss in later stage disease. Based on the clinial histopathological properties of the deposits, corneal dystrophy can be divided into two main types: lattice corneal dystrophy (LCD) and granular corneal dystrophy (GCD). These two types of corneal dystrophies are further divided into subtypes according to the differences in the clinical features of the disease. So far, 33 mutations have been identified in the TGFBI gene associated with all the GCDs and most of the LCDs, with two major mutational sites Arg124 and Arg555, accounting for more than half of all the patients with the disease.

Implicated in

Entity name
Colon Cancer
Prognosis
Colon cancers associated with overexpression of TGFBI may have an increased metastatic potential, leading to poor prognosis in cancer patients.
Oncogenesis
Upregulation of TGFBI is associated with high-grade human colon cancers. We have found that TGFBI promotes extravasation, a critical step in the metastatic dissemination of cancer cells, by inducing the dissociation of VE-cadherin junctions between endothelial cells via activation of the integrin alphavbeta5-Src signaling pathway.
Entity name
Pancreatic Cancer
Oncogenesis
TGFBI was found induced by TGFbeta1 in pancreatic cancer cell lines (CAPAN-1, PANC-1). In human pancreatic tissues, TGFBI was 32.4 fold upregulated in pancreatic cancers in comparison to normal control tissues at mRNA level.
Entity name
Ovarian Cancer
Oncogenesis
Loss of TGFBI induce specific resistance to paclitaxel and mitotic spindle abnormalities in ovarian cancer cells. TGFBI expression restores the paclitaxel sensitivity via FAK- and RHO- dependent stabilization of microtubules.
Entity name
Lung Cancer
Oncogenesis
TGFBI protein was absent or reduced in 45 of 130 primary lung carcinomas in comparison to normal lung tissues.
Entity name
Neuroblastoma
Oncogenesis
Enhanced expression of TGFBI in human neuroblastoma cells suppresses neuroblastoma cell cohesion and adhesion to various ECM proteins. TGFBI also inhibits neuroblastoma cell proliferation and invasion.
Entity name
Liver Cancer
Oncogenesis
TGFBI expression promotes cell adhesion, invasion and MMP secretion of human hepatoma cell line SMMC-7721.

Bibliography

Pubmed IDLast YearTitleAuthors
180686292007The extracellular matrix protein TGFBI induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel.Ahmed AA et al
167074572006Keratoepithelin suppresses the progression of experimental human neuroblastomas.Becker J et al
120347052002The transforming growth factor-beta-inducible matrix protein (beta)ig-h3 interacts with fibronectin.Billings PC et al
187796582008Expression patterns of betaig-h3 in chondrocyte differentiation during endochondral ossification.Han MS et al
90610011997Characterization of a cartilage-derived 66-kDa protein (RGD-CAP/beta ig-h3) that binds to collagen.Hashimoto K et al
185607602008TGFbeta-induced protein mediates lymphatic endothelial cell adhesion to the extracellular matrix under low oxygen conditions.Irigoyen M et al
166832552006TGFBI gene mutations in corneal dystrophies.Kannabiran C et al
180836242008Transforming growth factor-beta-induced gene product, as a novel ligand of integrin alphaMbeta2, promotes monocytes adhesion, migration and chemotaxis.Kim HJ et al
182454462008Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation.Ma C et al
164344042006Beta ig-h3 interacts directly with biglycan and decorin, promotes collagen VI aggregation, and participates in ternary complexing with these macromolecules.Reinboth B et al
123793072002Induction and expression of betaig-h3 in pancreatic cancer cells.Schneider D et al
13887241992cDNA cloning and sequence analysis of beta ig-h3, a novel gene induced in a human adenocarcinoma cell line after treatment with transforming growth factor-beta.Skonier J et al
163291462006Loss of Betaig-h3 protein is frequent in primary lung carcinoma and related to tumorigenic phenotype in lung cancer cells.Zhao Y et al

Other Information

Locus ID:

NCBI: 7045
MIM: 601692
HGNC: 11771
Ensembl: ENSG00000120708

Variants:

dbSNP: 7045
ClinVar: 7045
TCGA: ENSG00000120708
COSMIC: TGFBI

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000120708ENST00000442011Q15582
ENSG00000120708ENST00000442011A0A0S2Z4Q2
ENSG00000120708ENST00000503087H0YAH8
ENSG00000120708ENST00000507018H0Y8M8
ENSG00000120708ENST00000508076D6RBX4
ENSG00000120708ENST00000508767H0Y9D7
ENSG00000120708ENST00000509485H0YAB8
ENSG00000120708ENST00000514554H0Y8L3
ENSG00000120708ENST00000604555S4R3C6

Expression (GTEx)

0
500
1000
1500
2000
2500
3000

Pathways

PathwaySourceExternal ID
Metabolism of proteinsREACTOMER-HSA-392499
Amyloid fiber formationREACTOMER-HSA-977225

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
249889462014lncRNA H19/miR-675 axis represses prostate cancer metastasis by targeting TGFBI.104
180686292007The extracellular matrix protein TGFBI induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel.86
182454462008Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation.85
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
119232332002BIGH3 mutation spectrum in corneal dystrophies.58
122709302002Identification of motifs in the fasciclin domains of the transforming growth factor-beta-induced matrix protein betaig-h3 that interact with the alphavbeta5 integrin.54
217207222012Target gene repression mediated by miRNAs miR-181c and miR-9 both of which are down-regulated by amyloid-β.48
246391952014Integrins αvβ5 and αvβ3 promote latent TGF-β1 activation by human cardiac fibroblast contraction.46
127041922003Identification of the alphavbeta3 integrin-interacting motif of betaig-h3 and its anti-angiogenic effect.35
183542292008Macrophages produce TGF-beta-induced (beta-ig-h3) following ingestion of apoptotic cells and regulate MMP14 levels and collagen turnover in fibroblasts.35

Citation

Chaoyu Ma ; Xiao-Fan Wang

TGFBI (transforming growth factor, beta-induced, 68kDa)

Atlas Genet Cytogenet Oncol Haematol. 2009-02-01

Online version: http://atlasgeneticsoncology.org/gene/42539/tgfbi