LASP1 (LIM and SH3 protein)

Identity

Other names	MLN50, EVI149
HGNC	LASP1
Location	17q12-21
Local_order	from centromere to telomere are: TRAF4 (alias MLN62/CART1), MLLT6 (alias AF17), LASP1, STARD3 (alias MLN64), ERBB2 (alias c-erbB2), and RARA

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

Protein

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	t(11;17)(q23;q12) --> MLL-LASP1
Disease	infant AML-M4; only one case described so far
Abnormal 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	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

External links

	Nomenclature
HGNC	LASP1   6513
Entrez_Gene	LASP1  3927  LIM and SH3 protein 1
	Cards
Atlas	Lasp1ID203
GeneCards	LASP1
Ensembl	LASP1 [Search_View]   ENSG00000002834 [Gene_View]
Genatlas	LASP1
GeneLynx	LASP1
eGenome	LASP1
euGene	3927
	Genomic and cartography
GoldenPath	LASP1  -     chr17:34279894-34331541 +  17q11-q21.3   [Description]    (hg18-Mar_2006)
Ensembl	LASP1 - 17q11-q21.3 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	LASP1
	Gene and transcription
Genbank	AK095958 [ ENTREZ ]
Genbank	AK289847 [ ENTREZ ]
Genbank	AK307868 [ ENTREZ ]
Genbank	AK309933 [ ENTREZ ]
Genbank	BC007367 [ ENTREZ ]
RefSeq	NM_006148 [ SRS ]    NM_006148 [ ENTREZ ]
RefSeq	AC_000060 [ SRS ]    AC_000060 [ ENTREZ ]
RefSeq	AC_000149 [ SRS ]    AC_000149 [ ENTREZ ]
RefSeq	NC_000017 [ SRS ]    NC_000017 [ ENTREZ ]
RefSeq	NT_010755 [ SRS ]    NT_010755 [ ENTREZ ]
RefSeq	NW_001838435 [ SRS ]    NW_001838435 [ ENTREZ ]
RefSeq	NW_926828 [ SRS ]    NW_926828 [ ENTREZ ]
AceView	LASP1 AceView - NCBI
Unigene	Hs.548018 [ SRS ]    Hs.548018 [ NCBI ]     HS548018 [ spliceNest ]
Fast-db	9402 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q14847 [ SRS]    Q14847 [ EXPASY ]     Q14847 [ INTERPRO ]     Q14847 [ UNIPROT ]
Prosite	PS00478 LIM_DOMAIN_1 [ SRS ]    PS00478 LIM_DOMAIN_1 [ Expasy ]
Prosite	PS50023 LIM_DOMAIN_2 [ SRS ]    PS50023 LIM_DOMAIN_2 [ Expasy ]
Prosite	PS51216 NEBULIN [ SRS ]    PS51216 NEBULIN [ Expasy ]
Prosite	PS50002 SH3 [ SRS ]    PS50002 SH3 [ Expasy ]
Interpro	IPR013998 Nebulin [ SRS ]    IPR013998 Nebulin [ EBI ]
Interpro	IPR000900 Nebulin_35r-motif [ SRS ]    IPR000900 Nebulin_35r-motif [ EBI ]
Interpro	IPR001452 SH3 [ SRS ]    IPR001452 SH3 [ EBI ]
Interpro	IPR001781 Znf_LIM [ SRS ]    IPR001781 Znf_LIM [ EBI ]
CluSTr	Q14847
Pfam	PF00412 LIM [ SRS ]    PF00412 LIM [ Sanger ]    pfam00412 [ NCBI-CDD ]
Pfam	PF00880 Nebulin [ SRS ]    PF00880 Nebulin [ Sanger ]    pfam00880 [ NCBI-CDD ]
Pfam	PF00018 SH3_1 [ SRS ]    PF00018 SH3_1 [ Sanger ]    pfam00018 [ NCBI-CDD ]
Smart	SM00132 LIM [EMBL]
Smart	SM00227 NEBU [EMBL]
Smart	SM00326 SH3 [EMBL]
Prodom	PD000094 LIM[INRA-Toulouse]
Prodom	Q14847 LASP1_HUMAN [ Domain structure ]   Q14847 LASP1_HUMAN  [ sequences sharing at least 1 domain ]
Prodom	PD000094[INRA-Toulouse]
Prodom	Q14847 LASP1_HUMAN [ Domain structure ]   Q14847 LASP1_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	Q14847
HPRD	04229
	Protein Interaction databases
DIP	Q14847
IntAct	Q14847
	Polymorphism : SNP, mutations, diseases
OMIM	602920    [ map ]
GENECLINICS	602920
SNP	LASP1 [dbSNP-NCBI]
SNP	NM_006148 [SNP-NCI]
SNP	LASP1 [GeneSNPs - Utah]  LASP1] [HGBASE - SRS]
HAPMAP	LASP1 [HAPMAP]
TICdb	LASP1 [Translocation breakpoints In Cancer]
HGMD	LASP1
	General knowledge
Family Browser	LASP1 [UCSC Family Browser]
SOURCE	NM_006148
SMD	Hs.548018
SAGE	Hs.548018
GO	actin binding [Amigo]  actin binding
GO	SH3/SH2 adaptor activity [Amigo]  SH3/SH2 adaptor activity
GO	cytoplasm [Amigo]  cytoplasm
GO	cytoskeleton [Amigo]  cytoskeleton
GO	ion transport [Amigo]  ion transport
GO	zinc ion binding [Amigo]  zinc ion binding
GO	ion transmembrane transporter activity [Amigo]  ion transmembrane transporter activity
GO	cortical actin cytoskeleton [Amigo]  cortical actin cytoskeleton
GO	cortical cytoskeleton organization and biogenesis [Amigo]  cortical cytoskeleton organization and biogenesis
GO	metal ion binding [Amigo]  metal ion binding
PubGene	LASP1
TreeFam	LASP1
CTD	3927 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	LASP1 Related clones (RZPD - Berlin)
	PubMed
PubMed	17 Pubmed reference(s) in LocusLink

Bibliography

Lasp-1 (MLN 50) defines a new LIM protein subfamily characterized by the association of LIM and SH3 domains.

Tomasetto C, Moog-Lutz C, R��gnier CH, Schreiber V, Basset P, Rio MC

FEBS letters. 1995 ; 373 (3) : 245-249.

PMID 7589475

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, R��gnier C, Moog-Lutz C, Mattei MG, Chenard MP, Lidereau R, Basset P, Rio MC

Genomics. 1995 ; 28 (3) : 367-376.

PMID 7490069

Two distinct amplified regions at 17q11-q21 involved in human primary breast cancer.

Bi��che I, Tomasetto C, R��gnier CH, Moog-Lutz C, Rio MC, Lidereau R

Cancer research. 1996 ; 56 (17) : 3886-3890.

PMID 8752152

Lasp-1 is a regulated phosphoprotein within the cAMP signaling pathway in the gastric parietal cell.

Chew CS, Parente JA Jr, Zhou C, Baranco E, Chen X

The American journal of physiology. 1998 ; 275 (1 Pt 1) : C56-C67.

PMID 9688835

Chromosomal assignment and expression pattern of the murine Lasp-1 gene.

Schreiber V, Masson R, Linares JL, Mattei MG, Tomasetto C, Rio MC

Gene. 1998 ; 207 (2) : 171-175.

PMID 9511759

Lasp-1, a novel type of actin-binding protein accumulating in cell membrane extensions.

Schreiber V, Moog-Lutz C, R��gnier CH, Chenard MP, Boeuf H, Vonesch JL, Tomasetto C, Rio MC

Molecular medicine (Cambridge, Mass.). 1998 ; 4 (10) : 675-687.

PMID 9848085

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, Parente JA Jr, Chen X, Chaponnier C, Cameron RS

Journal of cell science. 2000 ; 113 ( Pt 11) : 2035-2045.

PMID 10806114

Lasp-1 binds to non-muscle F-actin in vitro and is localized within multiple sites of dynamic actin assembly in vivo.

Chew CS, Chen X, Parente JA Jr, Tarrer S, Okamoto C, Qin HY

Journal of cell science. 2002 ; 115 (Pt 24) : 4787-4799.

PMID 12432067

Actin binding of human LIM and SH3 protein is regulated by cGMP- and cAMP-dependent protein kinase phosphorylation on serine 146.

Butt E, Gambaryan S, G��ttfert N, Galler A, Marcus K, Meyer HE

The Journal of biological chemistry. 2003 ; 278 (18) : 15601-15607.

PMID 12571245

The human LASP1 gene is fused to MLL in an acute myeloid leukemia with t(11;17)(q23;q21).

Strehl S, Borkhardt A, Slany R, Fuchs UE, K��nig M, Haas OA

Oncogene. 2003 ; 22 (1) : 157-160.

PMID 12527918

Phosphorylation of mouse LASP-1 on threonine 156 by cAMP- and cGMP-dependent protein kinase.

Keicher C, Gambaryan S, Schulze E, Marcus K, Meyer HE, Butt E

Biochemical and biophysical research communications. 2004 ; 324 (1) : 308-316.

PMID 15465019

Zyxin interacts with the SH3 domains of the cytoskeletal proteins LIM-nebulette and Lasp-1.

Li B, Zhuang L, Trueb B

The Journal of biological chemistry. 2004 ; 279 (19) : 20401-20410.

PMID 15004028

Regulation of cell migration and survival by focal adhesion targeting of Lasp-1.

Lin YH, Park ZY, Lin D, Brahmbhatt AA, Rio MC, Yates JR 3rd, Klemke RL

The Journal of cell biology. 2004 ; 165 (3) : 421-432.

PMID 15138294

Actin-binding proteins in a postsynaptic preparation: Lasp-1 is a component of central nervous system synapses and dendritic spines.

Phillips GR, Anderson TR, Florens L, Gudas C, Magda G, Yates JR 3rd, Colman DR

Journal of neuroscience research. 2004 ; 78 (1) : 38-48.

PMID 15372503

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	03-2000	Marie-Christine Rio
		I.G.B.M.C., BP163, 1 rue Laurent Fries, 67404 ILLKIRCH, France
Updated	08-2005	Sabine Strehl

Citation

This paper should be referenced as such :

Rio MC . LASP1 (LIM and SH3 protein). Atlas Genet Cytogenet Oncol Haematol. March 2000 . URL : http://AtlasGeneticsOncology.org/Genes/Lasp1ID203.html

Strehl S . LASP1 (LIM and SH3 protein). Atlas Genet Cytogenet Oncol Haematol. August 2005 . URL : http://AtlasGeneticsOncology.org/Genes/Lasp1ID203.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:15:08 2008