CAPG (capping protein (actin filament), gelsolin-like)

2009-11-01 Peeyush Kumar Singh , Ranjan Tamuli Affiliation

Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati-781 039, Assam, India

Identity

HGNC

CAPG

LOCATION

2p11.2

LOCUSID

822

ALIAS

AFCP,HEL-S-66,MCP

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

DNA size: 15.58 kb; mRNA size: 1220 bp; 10 exons.

Proteins

Description

348 amino acids; 38.518 kDa. CapG protein contains three gelsolin-like repeats in the position 27-75 (49), 148-188 (41), and 261-307 (47); and a nuclear localization signal (NES) 137-146 (10). Three natural variants, VAR-047776 (V41I), VAR-047777 (R198W), and VAR-047778 (R335H) have been reported.
Isoforms: Altogether 15 different isoforms (eight complete, one COOH complete, and six partial) have been predicted. Isoform jApr07 is annotated, contains 79 amino acids N-terminal to the first AUG.

Expression

Ubiquitously expressed; highly expressed in prostate, lung, and kidney.

Localisation

Cytoplasmic (52.2 %), cytoskeletal (21.7 %), and nuclear (13.0 %), according to PSORT II prediction.

Function

CAPG encodes a member of the gelsolin/villin family of actin-regulatory proteins that reversibly blocks (capping) the barbed ends of F-actin filaments in a Ca²⁺and phosphoinositide-regulated manner, but does not sever preformed actin filaments. Capping contributes to the control of actin-based motility in non-muscle cells. Dysregulation of actin-based motility is a prominent factor in cell transformation and is probably associated with carcinogenesis. CAPG is also involved in cell signaling, receptor-mediated membrane ruffling, and phagocytosis.

Homology

The percent identity below represents identity of CAPG over an aligned region in UniGene.
- Pan troglodytes: 99.7 % (percentage identity)
- Macaca mulatta: 99.7 %
- Mus musculus: 95.4 %
- Rattus norvegicus: 92.8 %
- Bos taurus: 91.1 %
- Danio rerio: 61.7 %

Implicated in

Entity name

Breast cancer

Disease

CAPG is expressed at higher levels in metastasizing breast cancer, than in normal breast epithelium. Furthermore, CapG protein is also transported more rapidly into the nucleus of the breast cancerous cells than the corresponding benign cells. CapG knockdown reduces invasiveness in Matrigel invasion assay, which supports the role of CAPG in cell motility. Thus, increased expression of CAPG leads to dysregulation of cell motility that promotes tumor invasion.

Entity name

Oral carcinogenesis

Note

Significant overexpression of CapG protein was detected in oral squamous-cell carcinoma cells (OSCCs) and oral premalignant lesions (OPLs). Enhanced expression of CapG was also associated with large tumour size and advanced staging of OSCCs. Therefore, CapG may initiate or activate the neoplastic process of OSCC cells including the regulation of biologic behaviour of aggressive forms of cells rather than as a suppressor.

Entity name

Ovarian carcinomas

Disease

In a Swedish women population, CAPG was expressed more in tumors among deceased patients than survivors with ovarian carcinomas. The stage III serous papillary adenocarcinomas of the ovary show higher CAPG expression and this is possibly correlated with the advance disease stage. Overexpression of CAPG promotes aggressive tumor progression.

Entity name

Pancreatic cancer

Note

Up regulation and multiple isoforms of CapG were detected in pancreatic cancer tissue and cell lines. High level of CapG protein may possibly play an important role in pancreatic cancer cell motility and consequently dissemination.

Entity name

Ocular melanoma

Note

CapG, which is a unique regulator of the actin cytoskeleton, is expressed in malignant melanomas of the uvea but not to a significant extent in normal uveal melanocytes.

Entity name

Tumorigenic progression in cell lines

Note

Expression of the CapG protein was lost in the tumorigenic cell line, isolated from a human diploid fibroblast lineage. The CapG protein expression was lost also in cancer cell lines including stomach cancer, lung cancer and melanoma. The human stomach cancer cell line AZ 521 became non-tumorigenic after the introduction of CapG cDNA. Moreover, CapG expression was repressed in small-cell lung cancer tissues. These results indicate that CapG is a tumor suppressor gene involved in the tumorigenic progression of certain cancers.

Bibliography

Pubmed ID	Last Year	Title	Authors
1322908	1992	Molecular cloning of human macrophage capping protein cDNA. A unique member of the gelsolin/villin family expressed primarily in macrophages.	Dabiri GA et al
18237446	2008	Clinical significance of gelsolin-like actin-capping protein expression in oral carcinogenesis: an immunohistochemical study of premalignant and malignant lesions of the oral cavity.	Nomura H et al
18709641	2008	Four potential biomarkers as prognostic factors in stage III serous ovarian adenocarcinomas.	Partheen K et al
12754261	2003	Cap G, a gelsolin family protein modulating protective effects of unidirectional shear stress.	Pellieux C et al
18059028	2008	Invasive breast cancer cells exhibit increased mobility of the actin-binding protein CapG.	Renz M et al
16847067	2007	Pancreatic cancer cells overexpress gelsolin family-capping proteins, which contribute to their cell motility.	Thompson CC et al
9920419	1998	The identification and differential expression of calcium-binding proteins associated with ocular melanoma.	Van Ginkel PR et al
16767159	2006	Suppression of tumorigenicity, but not anchorage independence, of human cancer cells by new candidate tumor suppressor gene CapG.	Watari A et al

Other Information

Locus ID:

NCBI: 822
MIM: 153615
HGNC: 1474
Ensembl: ENSG00000042493

Variants:

dbSNP: 822
ClinVar: 822
TCGA: ENSG00000042493
COSMIC: CAPG

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000042493	ENST00000263867	P40121
ENSG00000042493	ENST00000263867	V9HW69
ENSG00000042493	ENST00000409275	B8ZZL6
ENSG00000042493	ENST00000409670	P40121
ENSG00000042493	ENST00000409670	V9HW69
ENSG00000042493	ENST00000409724	P40121
ENSG00000042493	ENST00000409724	V9HW69
ENSG00000042493	ENST00000409921	P40121
ENSG00000042493	ENST00000439385	E7ENU9
ENSG00000042493	ENST00000447219	E7ENU9
ENSG00000042493	ENST00000449030	E7ENU9
ENSG00000042493	ENST00000453973	H7C0X8

Expression (GTEx)

100

150

200

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

PharmGKB

Entity ID	Name	Type	Evidence	Association	PD
PA443937	Drug Toxicity	Disease	ClinicalAnnotation	associated	PD
PA446975	Neurotoxicity Syndromes	Disease	ClinicalAnnotation	associated	PD
PA451879	vincristine	Chemical	ClinicalAnnotation	associated	PD

References

Pubmed ID	Year	Title	Citations
19011242	2009	Integrin alpha6beta4 controls the expression of genes associated with cell motility, invasion, and metastasis, including S100A4/metastasin.	62
18709641	2008	Four potential biomarkers as prognostic factors in stage III serous ovarian adenocarcinomas.	30
15454578	2004	Increased importin-beta-dependent nuclear import of the actin modulating protein CapG promotes cell invasion.	22
21768101	2011	Muscle creatine kinase deficiency triggers both actin depolymerization and desmin disorganization by advanced glycation end products in dilated cardiomyopathy.	22
26757732	2016	CAPG and GIPC1: Breast Cancer Biomarkers for Bone Metastasis Development and Treatment.	22
16767159	2006	Suppression of tumorigenicity, but not anchorage independence, of human cancer cells by new candidate tumor suppressor gene CapG.	16
26466680	2015	CARMIL2 is a novel molecular connection between vimentin and actin essential for cell migration and invadopodia formation.	16
24804218	2014	Macrophage capping protein CapG is a putative oncogene involved in migration and invasiveness in ovarian carcinoma.	13
12637565	2003	The Nucleo-cytoplasmic actin-binding protein CapG lacks a nuclear export sequence present in structurally related proteins.	12
18059028	2008	Invasive breast cancer cells exhibit increased mobility of the actin-binding protein CapG.	12

Citation

Peeyush Kumar Singh ; Ranjan Tamuli

CAPG (capping protein (actin filament), gelsolin-like)

Atlas Genet Cytogenet Oncol Haematol. 2009-11-01

Online version: http://atlasgeneticsoncology.org/gene/44449/capg