TAGLN (transgelin)

2010-09-01 Stephen Assinder Affiliation

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

Identity

HGNC

TAGLN

LOCATION

11q23.3

LOCUSID

6876

ALIAS

SM22,SM22-alpha,SMCC,TAGLN1,WS3-10

FUSION GENES

Show Gene Fusions

DNA/RNA

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

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).

Article Bibliography

Pubmed ID	Last Year	Title	Authors
18378184	2009	Transgelin: an actin-binding protein and tumour suppressor.	Assinder SJ et al
9615232	1998	Expression and cytogenetic localization of the human SM22 gene (TAGLN).	Camoretti-Mercado B et al
12582250	2003	Smad proteins regulate transcriptional induction of the SM22alpha gene by TGF-beta.	Chen S et al
17464194	2007	SM22alpha is required for agonist-induced regulation of contractility: evidence from SM22alpha knockout mice.	Je HD et al
9384215	1997	Fibroblast transgelin and smooth muscle SM22alpha are the same protein, the expression of which is down-regulated in many cell lines.	Lawson D et al
3818630	1987	Isolation and characterization of an abundant and novel 22-kDa protein (SM22) from chicken gizzard smooth muscle.	Lees-Miller JP et al
16835221	2006	Expression cloning identifies transgelin (SM22) as a novel repressor of 92-kDa type IV collagenase (MMP-9) expression.	Nair RR et al
20012321	2010	Expression of the actin-associated protein transgelin (SM22) is decreased in prostate cancer.	Prasad PD et al
11773051	2002	Loss 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
17082327	2007	Transgelin 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 ID	Transcript ID	Uniprot
ENSG00000149591	ENST00000278968	Q01995
ENSG00000149591	ENST00000278968	Q5U0D2
ENSG00000149591	ENST00000392951	Q01995
ENSG00000149591	ENST00000392951	Q5U0D2
ENSG00000149591	ENST00000525531	Q01995
ENSG00000149591	ENST00000525531	Q5U0D2
ENSG00000149591	ENST00000529622	H0YCU9
ENSG00000149591	ENST00000529792	E9PJ32
ENSG00000149591	ENST00000530649	Q01995
ENSG00000149591	ENST00000530649	Q5U0D2
ENSG00000149591	ENST00000532870	Q01995
ENSG00000149591	ENST00000532870	Q5U0D2

Expression (GTEx)

1000

2000

3000

4000

5000

6000

7000

8000

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
37203411	2023	Transgelin promotes ferroptosis to inhibit the malignant progression of esophageal squamous cell carcinoma.	0
37290124	2023	Hypoxia-Inducible Factor-1α in SM22α-Expressing Cells Modulates Alveolarization.	1
37806182	2023	LZTS3/TAGLN Suppresses Cancer Progression in Human Colorectal Adenocarcinoma Through Regulating Cell Proliferation, Migration, and Actin Cytoskeleton.	0
37847687	2023	Loss of prolyl hydroxylase 1 and 2 in SM22α-expressing cells prevents Hypoxia-Induced pulmonary hypertension.	1
37203411	2023	Transgelin promotes ferroptosis to inhibit the malignant progression of esophageal squamous cell carcinoma.	0
37290124	2023	Hypoxia-Inducible Factor-1α in SM22α-Expressing Cells Modulates Alveolarization.	1
37806182	2023	LZTS3/TAGLN Suppresses Cancer Progression in Human Colorectal Adenocarcinoma Through Regulating Cell Proliferation, Migration, and Actin Cytoskeleton.	0
37847687	2023	Loss of prolyl hydroxylase 1 and 2 in SM22α-expressing cells prevents Hypoxia-Induced pulmonary hypertension.	1
35776288	2022	RNA-sequencing of human aortic valves identifies that miR-629-3p and TAGLN miRNA-mRNA pair involving in calcified aortic valve disease.	4
35776288	2022	RNA-sequencing of human aortic valves identifies that miR-629-3p and TAGLN miRNA-mRNA pair involving in calcified aortic valve disease.	4
33771884	2021	TAGLN Is Downregulated by TRAF6-Mediated Proteasomal Degradation in Prostate Cancer Cells.	5
33961858	2021	m(6)A demethylase ALKBH5 suppresses proliferation and migration of enteric neural crest cells by regulating TAGLN in Hirschsprung's disease.	6
34001947	2021	Identification of targets of JS-K against HBV-positive human hepatocellular carcinoma HepG2.2.15 cells with iTRAQ proteomics.	5
34338296	2021	The canonical smooth muscle cell marker TAGLN is present in endothelial cells and is involved in angiogenesis.	19
34538264	2021	TAGLN mediated stiffness-regulated ovarian cancer progression via RhoA/ROCK pathway.	21

Citation

Stephen Assinder

TAGLN (transgelin)

Atlas Genet Cytogenet Oncol Haematol. 2010-09-01

Online version: http://atlasgeneticsoncology.org/gene/46168/tagln-(transgelin)