TAGLN (transgelin)

2010-09-01   Stephen Assinder 

Physiology, School of Medical Sciences & Bosch Institute, F13 - Anderson Stuart Building, University of Sydney, Australia

Identity

HGNC
LOCATION
11q23.3
LOCUSID
ALIAS
SM22,SM22-alpha,SMCC,TAGLN1,WS3-10
FUSION GENES

DNA/RNA

Atlas Image
Figure 1. Gene structure showing 5 exonic regions (boxes) and 4 intronic regions (lines). Expanded promoter provides relative positions of promoters upstream (-) and downstream (+) of start site. CarG = serum response binding box; TCE = TGF-beta control element; SBE = Smad binding element. Resulting transcript is given, with 5 and 3 UTRs (broken line) and translated region (solid line).

Description

5.4 kb gene located on 11q23.2 consisting of 5 exons, a large intron 1 and 3 short introns. Several putative promoters present in 800 bp upstream region.

Transcription

A 1566 bp transcript is generated from TAGLN. All exon 1 and first 12 bp of exon 2 are untranslated. As are the last 432 bp of exon 5.

Proteins

Note

Translated protein sequence is:
MANKGPSYGMSREVQSKIEKKYDEELEERLVEWIIVQCGPDVGRPDRGRLGFQVWLKNGVILSKLVNSLY
PDGSKPVKVPENPPSMVFKQMEQVAQFLKAAEDYGVIKTDMFQTVDLFEGKDMAAVQRTLMALGSLAV
TKNDGHYRGDPNWFMKKAQEHKREFTESQLQEGKHVIGLQMGSNRGASQAGMTGYGRPRQIIS
Atlas Image
Figure 2. Primary protein structure with amino acid (aa) positions of the calponin homologue (CH) region with calcium binding site (EF-hand) and actin binding calponin-like (CLIK) region. CKII and PKC refer to putative caseine kinase II and protein kinase C phosphorylation sites respectively.

Description

A 201 aa peptide member of the calponin family of actin binding proteins by virtue of a N-terminal calponin homologue domain and a single C-terminal calponin-like module. This C-terminal CLIK is required for actin binding.

Expression

Expression profiles are a point of debate. It is found throughout normal smooth muscle of adult vertebrates. It is also found outside of smooth muscle in the spinal chord, adrenal gland and heart, mesenchymal cells and fibroblasts, epithelium of the intestine, glomerular, breast and prostate.

Localisation

It is localised to the cytosol where it binds to F-actin.

Function

Transgelin is an actin stress fibre binding protein. It gels and stabilises actin gels. In the embryo it is involved in podosome formation and myocyte migration, vascular and visceral smooth muscle cell differentiation, and in the suppression of matrix metallo protease 9 (MMP9) where it is thought to be involved in the suppression of tissue re-modelling following muscle cell differentiation. Similarly in the adult, it is thought to suppress tumour cell invasion through MMP-9 suppression. Furthermore, it has been reported to suppress translocation of androgen receptor to the nucleus. Its expression is down-regulated in many cell lines, and this may be an early marker of the onset of transformation. Indeed it is becoming increasingly evident that transgelin may act as a tumour suppressor.

Implicated in

Entity name
Various cancers
Note
Disorganisation of the actin cytoskeleton is a fundamental event of the developing cancer cell phenotype. Transgelin is one of several proteins that bind actin and subsequently cross-link and bundle filaments into stress fibres. Expression is decreased in prostate, breast and colon cancers.
Entity name
Prostate cancer
Note
Transgelin is one of the 2% most significant of all down regulated genes in prostate cancer. Its expression has been shown to decrease with disease progression with lowest expression in metastasised lesions. Loss of transgelin may be significant to suppression of androgen induced proliferation of androgen dependant prostate cancer as it prevents binding of a co-activator to androgen receptor, thereby blocking nuclear translocation and resulting in suppression of androgen mediated cell growth. Recent studies suggest that transgelin promotes p53 mediated mitochondrial dependent apotptosis. Indeed coimmunoprecipitation and two hybrid studies have shown p53 and transgelin to be binding partners, with re-expression of transgelin promoting cytoplasmic p53 translocation in the prostate cancer cell line LNCaP. The value of transgelin as a target for selenium treatment has very recently been highlighted in a mouse model of prostate cancer (TRAMP mouse) where transgelin is increased with an associated decrease in tumour development.
Prognosis
Unknown.
Entity name
Colorectal cancer
Note
Loss of transgelin is closely associated with progression, differentiation and metastasis of colon cancer. Restoration of transgelin expression both in vitro and in vivo inhibits carcinogenesis. Decreased expression of transgelin in patients with colorectal cancer is associated with elevated levels of anti-transgelin antibodies, particularly during later stages, and subsequently with lower survival.
Prognosis
Decreased transgelin is associated with poor prognosis.
Entity name
Breast cancer
Note
Expression of transgelin occurs early in the disease process, possibly through constitutive ras activation.
Prognosis
Unknown.
Entity name
Ischaemic heart disease and vascular inflammation
Note
Coronary arteries of the ischemic heart display increased abundance of transgelin. In TAGLN null mice inflammatory response is increased following carotid artery injury. It is suggested that transgelin suppresses pro-inflamatory NF kappa B and oxidative stress (via suppression of superoxide dismutase and p47 phox).

Bibliography

Pubmed IDLast YearTitleAuthors
183781842009Transgelin: an actin-binding protein and tumour suppressor.Assinder SJ et al
96152321998Expression and cytogenetic localization of the human SM22 gene (TAGLN).Camoretti-Mercado B et al
125822502003Smad proteins regulate transcriptional induction of the SM22alpha gene by TGF-beta.Chen S et al
174641942007SM22alpha is required for agonist-induced regulation of contractility: evidence from SM22alpha knockout mice.Je HD et al
93842151997Fibroblast transgelin and smooth muscle SM22alpha are the same protein, the expression of which is down-regulated in many cell lines.Lawson D et al
38186301987Isolation and characterization of an abundant and novel 22-kDa protein (SM22) from chicken gizzard smooth muscle.Lees-Miller JP et al
168352212006Expression cloning identifies transgelin (SM22) as a novel repressor of 92-kDa type IV collagenase (MMP-9) expression.Nair RR et al
200123212010Expression of the actin-associated protein transgelin (SM22) is decreased in prostate cancer.Prasad PD et al
117730512002Loss of transgelin in breast and colon tumors and in RIE-1 cells by Ras deregulation of gene expression through Raf-independent pathways.Shields JM et al
170823272007Transgelin functions as a suppressor via inhibition of ARA54-enhanced androgen receptor transactivation and prostate cancer cell growth.Yang Z et al

Other Information

Locus ID:

NCBI: 6876
MIM: 600818
HGNC: 11553
Ensembl: ENSG00000149591

Variants:

dbSNP: 6876
ClinVar: 6876
TCGA: ENSG00000149591
COSMIC: TAGLN

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000149591ENST00000278968Q01995
ENSG00000149591ENST00000278968Q5U0D2
ENSG00000149591ENST00000392951Q01995
ENSG00000149591ENST00000392951Q5U0D2
ENSG00000149591ENST00000525531Q01995
ENSG00000149591ENST00000525531Q5U0D2
ENSG00000149591ENST00000529622H0YCU9
ENSG00000149591ENST00000529792E9PJ32
ENSG00000149591ENST00000530649Q01995
ENSG00000149591ENST00000530649Q5U0D2
ENSG00000149591ENST00000532870Q01995
ENSG00000149591ENST00000532870Q5U0D2

Expression (GTEx)

0
1000
2000
3000
4000
5000
6000
7000
8000

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
183781842009Transgelin: an actin-binding protein and tumour suppressor.73
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
117730512002Loss of transgelin in breast and colon tumors and in RIE-1 cells by Ras deregulation of gene expression through Raf-independent pathways.42
190111512009Myosin, transgelin, and myosin light chain kinase: expression and function in asthma.42
182451742008Transgelin is a direct target of TGF-beta/Smad3-dependent epithelial cell migration in lung fibrosis.38
198484162009Tissue proteomics reveals differential and compartment-specific expression of the homologs transgelin and transgelin-2 in lung adenocarcinoma and its stroma.32
197246802009Association of the actin-binding protein transgelin with lymph node metastasis in human colorectal cancer.31
207074032010Transgelin promotes migration and invasion of cancer stem cells.31
170823272007Transgelin functions as a suppressor via inhibition of ARA54-enhanced androgen receptor transactivation and prostate cancer cell growth.28

Citation

Stephen Assinder

TAGLN (transgelin)

Atlas Genet Cytogenet Oncol Haematol. 2010-09-01

Online version: http://atlasgeneticsoncology.org/gene/46168/tagln