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

Written2009-02Chaoyu Ma, Xiao-Fan Wang
Dept of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA

(Note : for Links provided by Atlas : click)


transforming growth factor, beta-induced, 68kD
transforming growth factor, beta-induced, 68kDa
Alias_symbol (synonym)BIGH3
Other aliasCDG2
LocusID (NCBI) 7045
Atlas_Id 42539
Location 5q31.1  [Link to chromosome band 5q31]
Location_base_pair Starts at 136028895 and ends at 136063818 bp from pter ( according to hg19-Feb_2009)  [Mapping TGFBI.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ABCC5 (3q27.1) / TGFBI (5q31.1)ANKS1B (12q23.1) / TGFBI (5q31.1)EIF4A2 (3q27.3) / TGFBI (5q31.1)
LMO7 (13q22.2) / TGFBI (5q31.1)LOC100507412 (-) / TGFBI (5q31.1)TGFBI (5q31.1) / CNPY3 (6p21.1)
TGFBI (5q31.1) / HLA-C (6p21.33)TGFBI (5q31.1) / MYH9 (22q12.3)TGFBI (5q31.1) / SH3PXD2A (10q24.33)
TGFBI (5q31.1) / TGFBI (5q31.1)TGFBI (5q31.1) / ZYX (7q34)


Description 19 exons.
Transcription 2.8 Kb mRNA, 2049 bp open reading frame.


  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.


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 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 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 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 Lung Cancer
Oncogenesis TGFBI protein was absent or reduced in 45 of 130 primary lung carcinomas in comparison to normal lung tissues.
Entity 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 Liver Cancer
Oncogenesis TGFBI expression promotes cell adhesion, invasion and MMP secretion of human hepatoma cell line SMMC-7721.


The extracellular matrix protein TGFBI induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel.
Ahmed AA, Mills AD, Ibrahim AE, Temple J, Blenkiron C, Vias M, Massie CE, Iyer NG, McGeoch A, Crawford R, Nicke B, Downward J, Swanton C, Bell SD, Earl HM, Laskey RA, Caldas C, Brenton JD.
Cancer Cell. 2007 Dec;12(6):514-27.
PMID 18068629
Keratoepithelin suppresses the progression of experimental human neuroblastomas.
Becker J, Erdlenbruch B, Noskova I, Schramm A, Aumailley M, Schorderet DF, Schweigerer L.
Cancer Res. 2006 May 15;66(10):5314-21.
PMID 16707457
The transforming growth factor-beta-inducible matrix protein (beta)ig-h3 interacts with fibronectin.
Billings PC, Whitbeck JC, Adams CS, Abrams WR, Cohen AJ, Engelsberg BN, Howard PS, Rosenbloom J.
J Biol Chem. 2002 Aug 2;277(31):28003-9. Epub 2002 May 28.
PMID 12034705
Expression patterns of betaig-h3 in chondrocyte differentiation during endochondral ossification.
Han MS, Kim JE, Shin HI, Kim IS.
Exp Mol Med. 2008 Aug 31;40(4):453-60.
PMID 18779658
Characterization of a cartilage-derived 66-kDa protein (RGD-CAP/beta ig-h3) that binds to collagen.
Hashimoto K, Noshiro M, Ohno S, Kawamoto T, Satakeda H, Akagawa Y, Nakashima K, Okimura A, Ishida H, Okamoto T, Pan H, Shen M, Yan W, Kato Y.
Biochim Biophys Acta. 1997 Mar 1;1355(3):303-14.
PMID 9061001
TGFbeta-induced protein mediates lymphatic endothelial cell adhesion to the extracellular matrix under low oxygen conditions.
Irigoyen M, Anso E, Salvo E, de las Herrerias JD, Martinez-Irujo JJ, Rouzaut A.
Cell Mol Life Sci. 2008 Jul;65(14):2244-55.
PMID 18560760
TGFBI gene mutations in corneal dystrophies.
Kannabiran C, Klintworth GK.
Hum Mutat. 2006 Jul;27(7):615-25. Review
PMID 16683255
Transforming growth factor-beta-induced gene product, as a novel ligand of integrin alphaMbeta2, promotes monocytes adhesion, migration and chemotaxis.
Kim HJ, Kim IS.
Int J Biochem Cell Biol. 2008;40(5):991-1004. Epub 2007 Nov 13.
PMID 18083624
Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation.
Ma C, Rong Y, Radiloff DR, Datto MB, Centeno B, Bao S, Cheng AW, Lin F, Jiang S, Yeatman TJ, Wang XF.
Genes Dev. 2008 Feb 1;22(3):308-21.
PMID 18245446
Beta ig-h3 interacts directly with biglycan and decorin, promotes collagen VI aggregation, and participates in ternary complexing with these macromolecules.
Reinboth B, Thomas J, Hanssen E, Gibson MA.
J Biol Chem. 2006 Mar 24;281(12):7816-24. Epub 2006 Jan 24.
PMID 16434404
Induction and expression of betaig-h3 in pancreatic cancer cells.
Schneider D, Kleeff J, Berberat PO, Zhu Z, Korc M, Friess H, Buchler MW.
Biochim Biophys Acta. 2002 Oct 9;1588(1):1-6.
PMID 12379307
cDNA 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, Neubauer M, Madisen L, Bennett K, Plowman GD, Purchio AF.
DNA Cell Biol. 1992 Sep;11(7):511-22.
PMID 1388724
Loss of Betaig-h3 protein is frequent in primary lung carcinoma and related to tumorigenic phenotype in lung cancer cells.
Zhao Y, El-Gabry M, Hei TK.
Mol Carcinog. 2006 Feb;45(2):84-92.
PMID 16329146


This paper should be referenced as such :
Ma, C ; Wang, XF
TGFBI (transforming growth factor, beta-induced, 68kDa)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(1):62-64.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(5;22)(q31;q12) TGFBI/MYH9

External links

HGNC (Hugo)TGFBI   11771
Entrez_Gene (NCBI)TGFBI  7045  transforming growth factor beta induced
AliasesBIGH3; CDB1; CDG2; CDGG1; 
GeneCards (Weizmann)TGFBI
Ensembl hg19 (Hinxton)ENSG00000120708 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000120708 [Gene_View]  ENSG00000120708 [Sequence]  chr5:136028895-136063818 [Contig_View]  TGFBI [Vega]
ICGC DataPortalENSG00000120708
Genatlas (Paris)TGFBI
Genetics Home Reference (NIH)TGFBI
Genomic and cartography
GoldenPath hg38 (UCSC)TGFBI  -     chr5:136028895-136063818 +  5q31.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TGFBI  -     5q31.1   [Description]    (hg19-Feb_2009)
EnsemblTGFBI - 5q31.1 [CytoView hg19]  TGFBI - 5q31.1 [CytoView hg38]
Mapping of homologs : NCBITGFBI [Mapview hg19]  TGFBI [Mapview hg38]
OMIM121820   121900   122200   601692   602082   607541   608470   608471   
Gene and transcription
Genbank (Entrez)AB209598 AK093916 AK094055 AK094581 AK222833
RefSeq transcript (Entrez)NM_000358
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)TGFBI
Cluster EST : UnigeneHs.369397 [ NCBI ]
CGAP (NCI)Hs.369397
Alternative Splicing GalleryENSG00000120708
Gene Expression Viewer (FireBrowse)TGFBI [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7045
GTEX Portal (Tissue expression)TGFBI
Human Protein AtlasENSG00000120708-TGFBI [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ15582   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ15582  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ15582
Splice isoforms : SwissVarQ15582
Domaine pattern : Prosite (Expaxy)EMI (PS51041)    FAS1 (PS50213)   
Domains : Interpro (EBI)EMI_domain    FAS1_domain    TGFBI    TGFBI/POSTN   
Domain families : Pfam (Sanger)Fasciclin (PF02469)   
Domain families : Pfam (NCBI)pfam02469   
Domain families : Smart (EMBL)FAS1 (SM00554)  
Conserved Domain (NCBI)TGFBI
DMDM Disease mutations7045
Blocks (Seattle)TGFBI
PDB (SRS)1X3B    2LTB    2LTC    2VXP   
PDB (PDBSum)1X3B    2LTB    2LTC    2VXP   
PDB (IMB)1X3B    2LTB    2LTC    2VXP   
PDB (RSDB)1X3B    2LTB    2LTC    2VXP   
Structural Biology KnowledgeBase1X3B    2LTB    2LTC    2VXP   
SCOP (Structural Classification of Proteins)1X3B    2LTB    2LTC    2VXP   
CATH (Classification of proteins structures)1X3B    2LTB    2LTC    2VXP   
Human Protein Atlas [tissue]ENSG00000120708-TGFBI [tissue]
Peptide AtlasQ15582
IPIIPI00018219   IPI00873923   IPI00965868   IPI00556324   IPI00940091   IPI00965607   IPI00965111   IPI00967087   IPI00966527   IPI00966279   
Protein Interaction databases
IntAct (EBI)Q15582
Ontologies - Pathways
Ontology : AmiGOangiogenesis  chondrocyte differentiation  integrin binding  protein binding  collagen binding  extracellular region  extracellular region  proteinaceous extracellular matrix  basement membrane  extracellular space  trans-Golgi network  plasma membrane  cell adhesion  negative regulation of cell adhesion  visual perception  cell proliferation  extracellular matrix organization  extracellular matrix  extracellular matrix  extracellular matrix  extracellular matrix  cellular protein metabolic process  extracellular matrix binding  response to stimulus  extracellular exosome  
Ontology : EGO-EBIangiogenesis  chondrocyte differentiation  integrin binding  protein binding  collagen binding  extracellular region  extracellular region  proteinaceous extracellular matrix  basement membrane  extracellular space  trans-Golgi network  plasma membrane  cell adhesion  negative regulation of cell adhesion  visual perception  cell proliferation  extracellular matrix organization  extracellular matrix  extracellular matrix  extracellular matrix  extracellular matrix  cellular protein metabolic process  extracellular matrix binding  response to stimulus  extracellular exosome  
REACTOMEQ15582 [protein]
REACTOME PathwaysR-HSA-977225 [pathway]   
Atlas of Cancer Signalling NetworkTGFBI
Wikipedia pathwaysTGFBI
Orthology - Evolution
GeneTree (enSembl)ENSG00000120708
Phylogenetic Trees/Animal Genes : TreeFamTGFBI
Homologs : HomoloGeneTGFBI
Homology/Alignments : Family Browser (UCSC)TGFBI
Gene fusions - Rearrangements
Fusion : MitelmanTGFBI/MYH9 [5q31.1/22q12.3]  
Fusion : QuiverTGFBI
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTGFBI [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TGFBI
Exome Variant ServerTGFBI
ExAC (Exome Aggregation Consortium)ENSG00000120708
GNOMAD BrowserENSG00000120708
Genetic variants : HAPMAP7045
Genomic Variants (DGV)TGFBI [DGVbeta]
DECIPHERTGFBI [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTGFBI 
ICGC Data PortalTGFBI 
TCGA Data PortalTGFBI 
Broad Tumor PortalTGFBI
OASIS PortalTGFBI [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTGFBI  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTGFBI
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TGFBI
DgiDB (Drug Gene Interaction Database)TGFBI
DoCM (Curated mutations)TGFBI (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TGFBI (select a term)
NCG5 (London)TGFBI
Cancer3DTGFBI(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM121820    121900    122200    601692    602082    607541    608470    608471   
Orphanet13973    13981    13980    13979    13978    13977   
Genetic Testing Registry TGFBI
NextProtQ15582 [Medical]
Target ValidationTGFBI
Huge Navigator TGFBI [HugePedia]
snp3D : Map Gene to Disease7045
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7045
Chemical/Pharm GKB GenePA36484
Clinical trialTGFBI
canSAR (ICR)TGFBI (select the gene name)
PubMed237 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon Jul 16 10:02:25 CEST 2018

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