LASP1 (LIM and SH3 protein)

2005-08-01 Sabine Strehl Affiliation

Childrens Cancer Research Institute, Kinderspitalgasse 6, A-1090 Vienna, Austria

Identity

HGNC

LASP1

LOCATION

17q12

LOCUSID

3927

ALIAS

Lasp-1,MLN50

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

LASP1 encompasses 51.65 kb on the genomic level and consists of 7 exons

Transcription

3845 bp mRNA, 783 bp coding sequence

Proteins

Description

261 amino acids; 29 kDa. LASP1 encodes a member of a LIM (Lin-11, Isl-1 and Mec-3) protein subfamily and is characterized by a LIM motif (cysteine-rich LIM/double zinc finger motif) at the N-terminus, an SH3 domain (Src homology region 3) at the C-terminus, and two actin-binding domains in the core of the protein

Expression

ubiquitous

Localisation

intracellular, cytoplasmic; associated with the F-actin rich cortical cytoskeleton

Function

LASP1 plays an important role in the regulation of dynamic actin-based, cytoskeletal activities and cell motility. Agonist-dependent changes in LASP1 phosphorylation may also serve to regulate actin-associated ion transport activities, not only in the parietal cell but also in certain other F-actin-rich secretory epithelial cell types. Together, (LIM-) nebulette, Lasp-1, and zyxin may play an important role in the organization of focal adhesions.

Homology

LASP family of proteins: actin-binding repeats similar to those in LASP1 are also present in other nebulin-related proteins such as NEBL (nebulette, 107 kD actin-binding Z-disk protein) and NRAP (nebulin-related anchoring protein); NRAP also contains an N-terminal LIM domain and NEB (nebulin) a C-terminal SH3 domain, both of which are highly homologous to the respective domains of LASP1.

Implicated in

Entity name

t(11;17)(q23;q12) --> KMT2A-LASP1

Disease

infant AML-M4; only one case described so far

Fusion protein

the MLL-LASP1 chimeric protein consists of the AT-hook DNA-binding domain and the methyltransferase motif including the CXXC zinc-finger domain of MLL and the SH3 domain of LASP1

Entity name

breast carcinomas

Disease

17q11-q21 amplification is found in about 25% of primary breast carcinomas; simultaneous amplification and overexpression of LASP1 and ERBB2

Prognosis

poor clinical outcome; increase risk of relapse

Bibliography

Pubmed ID	Last Year	Title	Authors
8752152	1996	Two distinct amplified regions at 17q11-q21 involved in human primary breast cancer.	Bièche I et al
12571245	2003	Actin binding of human LIM and SH3 protein is regulated by cGMP- and cAMP-dependent protein kinase phosphorylation on serine 146.	Butt E et al
12432067	2002	Lasp-1 binds to non-muscle F-actin in vitro and is localized within multiple sites of dynamic actin assembly in vivo.	Chew CS et al
10806114	2000	The LIM and SH3 domain-containing protein, lasp-1, may link the cAMP signaling pathway with dynamic membrane restructuring activities in ion transporting epithelia.	Chew CS et al
15465019	2004	Phosphorylation of mouse LASP-1 on threonine 156 by cAMP- and cGMP-dependent protein kinase.	Keicher C et al
15004028	2004	Zyxin interacts with the SH3 domains of the cytoskeletal proteins LIM-nebulette and Lasp-1.	Li B et al
15138294	2004	Regulation of cell migration and survival by focal adhesion targeting of Lasp-1.	Lin YH et al
15372503	2004	Actin-binding proteins in a postsynaptic preparation: Lasp-1 is a component of central nervous system synapses and dendritic spines.	Phillips GR et al
9848085	1998	Lasp-1, a novel type of actin-binding protein accumulating in cell membrane extensions.	Schreiber V et al
12527918	2003	The human LASP1 gene is fused to MLL in an acute myeloid leukemia with t(11;17)(q23;q21).	Strehl S et al
7490069	1995	Identification of four novel human genes amplified and overexpressed in breast carcinoma and localized to the q11-q21.3 region of chromosome 17.	Tomasetto C et al

Other Information

Locus ID:

NCBI: 3927
MIM: 602920
HGNC: 6513
Ensembl: ENSG00000002834

Variants:

dbSNP: 3927
ClinVar: 3927
TCGA: ENSG00000002834
COSMIC: LASP1

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000002834	ENST00000318008	Q14847
ENSG00000002834	ENST00000318008	A0A024R1S8
ENSG00000002834	ENST00000419929	C9J9W2
ENSG00000002834	ENST00000433206	Q14847
ENSG00000002834	ENST00000435347	Q14847
ENSG00000002834	ENST00000435347	A0A024R1S8
ENSG00000002834	ENST00000443937	F6S2S5
ENSG00000002834	ENST00000579123	J3KSN1
ENSG00000002834	ENST00000585841	K7ESD6

Expression (GTEx)

100

150

200

250

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
20379614	2010	Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.	62
22713668	2012	MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and LASP1 in human triple-negative breast cancer cells.	59
20660701	2010	Promotion of colorectal cancer growth and metastasis by the LIM and SH3 domain protein 1.	52
16430883	2006	Silencing of LASP-1 influences zyxin localization, inhibits proliferation and reduces migration in breast cancer cells.	47
24815849	2014	Tumor-suppressive microRNA-218 inhibits cancer cell migration and invasion via targeting of LASP1 in prostate cancer.	47
17211471	2007	Overexpression of LASP-1 mediates migration and proliferation of human ovarian cancer cells and influences zyxin localisation.	45
20843712	2012	Functional role of LASP1 in cell viability and its regulation by microRNAs in bladder cancer.	44
23968734	2013	miR-133a represses tumour growth and metastasis in colorectal cancer by targeting LIM and SH3 protein 1 and inhibiting the MAPK pathway.	44
25252758	2014	LIM and SH3 protein 1 induces TGFβ-mediated epithelial-mesenchymal transition in human colorectal cancer by regulating S100A4 expression.	40
12432067	2002	Lasp-1 binds to non-muscle F-actin in vitro and is localized within multiple sites of dynamic actin assembly in vivo.	39

Citation

Sabine Strehl

LASP1 (LIM and SH3 protein)

Atlas Genet Cytogenet Oncol Haematol. 2005-08-01

Online version: http://atlasgeneticsoncology.org/gene/203/lasp1

Historical Card

2000-03-01 LASP1 (LIM and SH3 protein) by Marie-Christine Rio Affiliation

I.G.B.M.C, 1, rue Laurent FRIES, BP 163 67404 ILLKIRH, France