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LASP1 (LIM and SH3 protein)

Identity

Other namesMLN50, EVI149
HGNC (Hugo) LASP1
Location 17q12-21
Location_base_pair Starts at 34279638 and ends at 34331548 bp from pter ( according to hg18-Mar_2006)  [Mapping]
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 (Hugo)LASP1   6513
Entrez_Gene (NCBI)LASP1  3927  LIM and SH3 protein 1
Cards
AtlasLasp1ID203
GeneCards (Weizmann)LASP1
Ensembl (Hinxton)ENSG00000002834 [Gene_View]  LASP1 [Vega]
AceView (NCBI)LASP1
Genatlas (Paris)LASP1
euGene (Indiana)3927
SOURCE (Stanford)NM_006148
Genomic and cartography
GoldenPath (UCSC)LASP1  -     chr17:34279638-34331548 +  17q11-q21.3   [Description]    (hg18-Mar_2006)
EnsemblLASP1 - 17q11-q21.3 [CytoView]
Mapping of homologs : NCBILASP1 [Mapview]
OMIM602920   
Gene and transcription
Gene : Genbank (Entrez)AK095958 AK289847 AK295522 AK296092 AK307868
Reference sequence (RefSeq transcript) :SRSNM_006148
Reference transcript : EntrezNM_006148
RefSeq genomic : SRSAC_000060 AC_000149 NC_000017 NT_010755 NW_001838435 NW_926828
RefSeq genomic : EntrezAC_000060 AC_000149 NC_000017 NT_010755 NW_001838435 NW_926828
Consensus coding sequences : CCDS NCBILASP1
Cluster EST : UnigeneHs.548018 [ SRS ] Hs.548018 [ NCBI ]
Alternative Splicing : Fast-db (Paris)9402
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtQ14847 (SRS) Q14847 (Expasy) Q14847 (Uniprot)
With graphics : InterProQ14847
Splice isoforms : VarSplice FASTAQ14847(VarSplice FASTA)
Domaine pattern : Prosite (SRS)LIM_DOMAIN_1 (PS00478)    LIM_DOMAIN_2 (PS50023)    NEBULIN (PS51216)    SH3 (PS50002)   
Domain pattern : Prosite (Expaxy)LIM_DOMAIN_1 (PS00478)    LIM_DOMAIN_2 (PS50023)    NEBULIN (PS51216)    SH3 (PS50002)   
Domains : Interpro (SRS)Nebulin    Nebulin_35r-motif    SH3    Znf_LIM   
Domains : Interpro (EBI)Nebulin    Nebulin_35r-motif    SH3    Znf_LIM   
Related proteins : CluSTrQ14847
Domain families : Pfam SRSLIM (PF00412)    Nebulin (PF00880)    SH3_1 (PF00018)   
Domain families : Pfam SangerLIM (PF00412)    Nebulin (PF00880)    SH3_1 (PF00018)   
Domain families : Pfam NCBIpfam00412    pfam00880    pfam00018   
Domain families : Smart EMBLLIM (SM00132)NEBU (SM00227)SH3 (SM00326)
Domain structure : Prodom (Prabi Lyon)LIM (PD000094)    (PD000094)   
Blocks (Seattle)Q14847
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD04229
Protein Interaction databases
DIP (DOE-UCLA)Q14847
IntAct (EBI)Q14847
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBILASP1
SNP : GeneSNP UtahLASP1
SNP : HGBaseLASP1
Genetic variants : HAPMAPLASP1
Translocation Breakpoints in Cancer : TICdbLASP1 
Mutations and Diseases : HGMDLASP1
Hereditary diseases : OMIM602920   
Hereditary diseases : GENETests602920   
Diseases : Genetic AssociationLASP1
General knowledge
Homologs : HomoloGeneLASP1
Homology/Alignments : Family Browser UCSCLASP1
Phylogenetic Trees/Animal Genes : TreeFamLASP1
Chemical/Protein Interactions : CTD3927
Keywords Ontology : AmiGOSH3/SH2 adaptor activity  protein binding  cytoplasm  cytoskeleton  focal adhesion  ion transport  zinc ion binding  ion transmembrane transporter activity  cortical actin cytoskeleton  cortical cytoskeleton organization  metal ion binding  actin filament binding  
Keywords Ontology : EGO-EBISH3/SH2 adaptor activity  protein binding  cytoplasm  cytoskeleton  focal adhesion  ion transport  zinc ion binding  ion transmembrane transporter activity  cortical actin cytoskeleton  cortical cytoskeleton organization  metal ion binding  actin filament binding  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
Probes : ImagenesLASP1 Related clones (RZPD - Berlin)
Literature
PubMed18 Pubmed reference(s) in Entrez
PubGeneLASP1

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, Rgnier 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, Rgnier 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.
Biche I, Tomasetto C, Rgnier 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, Rgnier 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, Gttfert 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, Knig 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 articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written03-2000Marie-Christine Rio
I.G.B.M.C., BP163, 1 rue Laurent Fries, 67404 ILLKIRCH, France
Updated08-2005Sabine 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

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indexed on : Sat Jun 27 16:37:32 CEST 2009

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