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LPP (lipoma preferred partner)

Written2004-05Marleen M Petit
Laboratory for Molecular Oncology, Department of Human Genetics, University of Leuven (K.U.Leuven) & VIB, Herestraat 49, B-3000 Leuven, Belgium

(Note : for Links provided by Atlas : click)

Identity

HGNC (Hugo) LPP
LocusID (NCBI) 4026
Atlas_Id 72
Location 3q28  [Link to chromosome band 3q28]
Location_base_pair Starts at 187943193 and ends at 188608460 bp from pter ( according to hg19-Feb_2009)  [Mapping LPP.png]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2016)
C12orf9 () / LPP (3q28)DLG1 (3q29) / LPP (3q28)DMD (Xp21.2) / LPP (3q28)
FAM19A3 (1p13.2) / LPP (3q28)HMGA2 (12q14.3) / LPP (3q28)KMT2A (11q23.3) / LPP (3q28)
LPP (3q28) / ABHD17C (15q25.1)LPP (3q28) / BCL6 (3q27.3)LPP (3q28) / C12orf9 ()
LPP (3q28) / CASR (3q21.1)LPP (3q28) / CD58 (1p13.1)LPP (3q28) / CHSY1 (15q26.3)
LPP (3q28) / CLSTN2 (3q23)LPP (3q28) / F2 (11p11.2)LPP (3q28) / GNL2 (1p34.3)
LPP (3q28) / GOLIM4 (3q26.2)LPP (3q28) / HMGA2 (12q14.3)LPP (3q28) / KMT2A (11q23.3)
LPP (3q28) / LPP (3q28)LPP (3q28) / LSM1 (8p11.23)LPP (3q28) / P3H2 (3q28)
LPP (3q28) / SPATA16 (3q26.31)LPP (3q28) / SSU72 (1p36.33)LPP (3q28) / ST6GAL1 (3q27.3)
LPP (3q28) / TP63 (3q28)LPP (3q28) / UBE2R2 (9p13.3)NCKIPSD (3p21.31) / LPP (3q28)
SEPT9 (17q25.2) / LPP (3q28)SFTPB (2p11.2) / LPP (3q28)TAGLN2 (1q23.2) / LPP (3q28)
TC2N (14q32.12) / LPP (3q28)

DNA/RNA

 
Description At least 11 exons; predicted start codon in exon 3, stop codon in exon 11; the protein coding region is covered by the overlapping "CEPH Mark 1" YAC clones 135H6 and 192B10 (start codon in 135H6, stop codon in 192B10) and is dispersed over at least 400 kb genomic DNA; the LIM domains are encoded by separate exons: LIM 1 is encoded by exon 8, LIM 2 by exon 9, and LIM 3 by exon 10 and part of exon 11.
Transcription mRNA: ubiquitously: > 10 kb; testis: additional transcripts of 1.8 kb and 1.25 kb
Pseudogene no pseudogenes

Protein

Description 612 amino acids; proline-rich region (amino-terminal 2/3 of the protein) followed by three LIM domains (carboxy-terminal 1/3 of the protein). Proline-rich region contains an alfa-actinin binding site, two VASP-binding motifs, and a nuclear export signal.
Expression Smooth muscle marker; readily detected on Western blot with an LPP-antibody in all fibroblastic and epithelial cell lines tested to date.
Localisation LPP is present in the cytoplasm of cells as well as at sites of cell adhesion such as focal adhesions (attachments sites to the extracellular matrix) and cell-cell contacts; LPP also shuttles to the nucleus and its nuclear-cytoplasmic localisation is regulated in part by a nuclear export signal (NES) which is sensitive to the drug leptomycin B.
Function Because of their structural features (many protein-protein interaction domains) and their characteristic to shuttle between the nucleus and the cytoplasm, LPP and its family members (see below) have been proposed to be scaffolding proteins involved in signal transduction from sites of cell adhesion to the nucleus; LPP has been shown to harbour transcriptional activation capacity in luciferase reporter assays, suggesting that LPP may be directly involved in the regulation of gene expression; LPP was found to be highly expressed in smooth muscle, and a role for LPP in regulating cell motility was proposed; the precise function of LPP remains to be elucidated.
Homology LPP is a member of the zyxin family of proteins, which contains five members: ajuba, LIMD1, LPP, TRIP6 and zyxin. The family hallmark of these proteins are three clustered LIM domains at the carboxy-terminus, which are protein interaction domains. All family members are present at sites of cell adhesion and have the ability to shuttle to the nucleus, and all family members have one or more nuclear export signals.

Mutations

Somatic HMGA2/LPP fusion proteins and MLL/LPP fusion proteins (Fig2).

Implicated in

Note
Entity solitary lipomas
Disease Benign tumors of adipose tissue.
Prognosis Can be surgically removed with no recurrence in most cases.
Cytogenetics More than 60% of solitary lipomas have an aberrant karyotype; 2/3 of these carry 12q15 rearrangements, most often translocations, affecting the HMGA2 gene; 1/4 of the latter have chromosomal region 3q27-q28 (containing LPP) as 12q15 translocation partner as such creating an HMGA2/LPP fusion gene.
Hybrid/Mutated Gene HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 8-11 or 9-11 of LPP; under the regulation of the HMGA2 promoter.
Abnormal Protein HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by two LIM domains (LIM 2 and LIM 3) or a portion of the proline-rich region and all three LIM domains of LPP.
 
  
Entity Pulmonary chondroid hamartomas
Disease Benign mesenchymal tumors of the lung.
Prognosis good
Cytogenetics More than 70% of pulmonary chondroid hamartomas have an aberrant karyotype; 70% of these carry 12q15 rearrangements, most often translocations, affecting the HMGA2 gene; 1/8 of the latter have chromosomal region 3q27-q28 (containing LPP) as 12q15 translocation partner as such creating an HMGA2/LPP fusion gene.
Hybrid/Mutated Gene HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 9-11 of LPP; under the regulation of the HMGA2 promoter.
Abnormal Protein HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP.
  
Entity Parosteal lipoma
Disease Rare deep-seated benign tumor of adipose tissue comprising less than 0.5% of all lipomas; parosteal lipomas exhibit a contiguous relationship with the periostium; because of their intimate relationship to the bone, they are considered as lipomas of bone.
Prognosis Most often asymptomatic; in some cases: loss of motor and/or sensory function as a result of the compression or stretching of a nerve.
Cytogenetics One case reported with rearrangement of LPP t(3;12)(q28;q14).
Hybrid/Mutated Gene HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 9-11 of LPP; under the regulation of the HMGA2 promoter.
Abnormal Protein HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP.
  
Entity Soft tissue chondroma
Disease Benign tumor of cartilage; rare entity.
Cytogenetics Only 31 cases with abnormal karyotypes have been reported (11-2003); 12q15 nonrandomly involved; one case reported with rearrangement of LPP t(3;12)(q27;q15).
Hybrid/Mutated Gene HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 9-11 of LPP; under the regulation of the HMGA2 promoter.
Abnormal Protein HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP.
  
Entity AML-M5
Disease Secondary leukemia following treatment with DNA topoisomerase II inhibitors.
Cytogenetics MLL gene on 11q23 frequently involved; one case reported with rearrangement of LPP t(3;11)(q28;q23).
Hybrid/Mutated Gene MLL/LPP hybrid gene containing the first 8 exons of MLL and exons 9-11 of LPP; under the regulation of the MLL promoter.
Abnormal Protein MLL/LPP fusion transcripts encode the three DNA-binding domains and the methyltransferase-like domain of MLL followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP.
  

Breakpoints

 

Bibliography

Human LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23).
Dahéron L, Veinstein A, Brizard F, Drabkin H, Lacotte L, Guilhot F, Larsen CJ, Brizard A, Roche J
Genes, chromosomes & cancer. 2001 ; 31 (4) : 382-389.
PMID 11433529
 
Fusion, disruption, and expression of HMGA2 in bone and soft tissue chondromas.
Dahlén A, Mertens F, Rydholm A, Brosjö O, Wejde J, Mandahl N, Panagopoulos I
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2003 ; 16 (11) : 1132-1140.
PMID 14614053
 
LPP, a LIM protein highly expressed in smooth muscle.
Gorenne I, Nakamoto RK, Phelps CP, Beckerle MC, Somlyo AV, Somlyo AP
American journal of physiology. Cell physiology. 2003 ; 285 (3) : C674-C685.
PMID 12760907
 
A novel LPP fusion gene indicates the crucial role of truncated LPP proteins in lipomas and pulmonary chondroid hamartomas.
Lemke I, Rogalla P, Bullerdiek J
Cytogenetics and cell genetics. 2001 ; 95 (3-4) : 153-156.
PMID 12063392
 
The lipoma preferred partner LPP interacts with alpha-actinin.
Li B, Zhuang L, Reinhard M, Trueb B
Journal of cell science. 2003 ; 116 (Pt 7) : 1359-1366.
PMID 12615977
 
Prediction of cell type-specific gene modules: identification and initial characterization of a core set of smooth muscle-specific genes.
Nelander S, Mostad P, Lindahl P
Genome research. 2003 ; 13 (8) : 1838-1854.
PMID 12869577
 
LPP, an actin cytoskeleton protein related to zyxin, harbors a nuclear export signal and transcriptional activation capacity.
Petit MM, Fradelizi J, Golsteyn RM, Ayoubi TA, Menichi B, Louvard D, Van de Ven WJ, Friederich E
Molecular biology of the cell. 2000 ; 11 (1) : 117-129.
PMID 10637295
 
The focal adhesion and nuclear targeting capacity of the LIM-containing lipoma-preferred partner (LPP) protein.
Petit MM, Meulemans SM, Van de Ven WJ
The Journal of biological chemistry. 2003 ; 278 (4) : 2157-2168.
PMID 12441356
 
LPP, the preferred fusion partner gene of HMGIC in lipomas, is a novel member of the LIM protein gene family.
Petit MM, Mols R, Schoenmakers EF, Mandahl N, Van de Ven WJ
Genomics. 1996 ; 36 (1) : 118-129.
PMID 8812423
 
Expression of reciprocal fusion transcripts of the HMGIC and LPP genes in parosteal lipoma.
Petit MM, Swarts S, Bridge JA, Van de Ven WJ
Cancer genetics and cytogenetics. 1998 ; 106 (1) : 18-23.
PMID 9772904
 
The t(3;12)(q27;q14-q15) with underlying HMGIC-LPP fusion is not determining an adipocytic phenotype.
Rogalla P, Kazmierczak B, Meyer-Bolte K, Tran KH, Bullerdiek J
Genes, chromosomes & cancer. 1998 ; 22 (2) : 100-104.
PMID 9598796
 

Citation

This paper should be referenced as such :
Petit, MM
LPP (lipoma preferred partner)
Atlas Genet Cytogenet Oncol Haematol. 2004;8(3):193-197.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/LPPID72.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(3;11)(q28;q23) KMT2A/LPP

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 5 ]
  Bone: Soft tissue chondroma with t(3;12)(q27;q15) HMGA2/LPP
Soft Tissues: Lipoma / benign lipomatous tumors
Soft Tissues: Ordinary lipoma with t(1;12)(p32;q14) HMGA2/PPAP2B
Soft tissue tumors: an overview
Lung: Translocations in Small Cell Carcinoma
Lung: Translocations in Squamous Cell Carcinoma

External links

Nomenclature
HGNC (Hugo)LPP   6679
Cards
AtlasLPPID72
Entrez_Gene (NCBI)LPP  4026  LIM domain containing preferred translocation partner in lipoma
Aliases
GeneCards (Weizmann)LPP
Ensembl hg19 (Hinxton)ENSG00000145012 [Gene_View]  chr3:187943193-188608460 [Contig_View]  LPP [Vega]
Ensembl hg38 (Hinxton)ENSG00000145012 [Gene_View]  chr3:187943193-188608460 [Contig_View]  LPP [Vega]
ICGC DataPortalENSG00000145012
TCGA cBioPortalLPP
AceView (NCBI)LPP
Genatlas (Paris)LPP
WikiGenes4026
SOURCE (Princeton)LPP
Genomic and cartography
GoldenPath hg19 (UCSC)LPP  -     chr3:187943193-188608460 +  3q27-q28   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)LPP  -     3q27-q28   [Description]    (hg38-Dec_2013)
EnsemblLPP - 3q27-q28 [CytoView hg19]  LPP - 3q27-q28 [CytoView hg38]
Mapping of homologs : NCBILPP [Mapview hg19]  LPP [Mapview hg38]
OMIM600700   
Gene and transcription
Genbank (Entrez)AA813328 AI126032 AK055214 AK123506 AK302959
RefSeq transcript (Entrez)NM_001167671 NM_001167672 NM_005578
RefSeq genomic (Entrez)NC_000003 NC_018914 NG_016932 NT_005612 NW_004929311
Consensus coding sequences : CCDS (NCBI)LPP
Cluster EST : UnigeneHs.720220 [ NCBI ]
CGAP (NCI)Hs.720220
Alternative Splicing GalleryENSG00000145012
Gene ExpressionLPP [ NCBI-GEO ]   LPP [ EBI - ARRAY_EXPRESS ]   LPP [ SEEK ]   LPP [ MEM ]
Gene Expression Viewer (FireBrowse)LPP [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4026
GTEX Portal (Tissue expression)LPP
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ93052 (Uniprot)
NextProtQ93052  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ93052
Splice isoforms : SwissVarQ93052 (Swissvar)
PhosPhoSitePlusQ93052
Domaine pattern : Prosite (Expaxy)LIM_DOMAIN_1 (PS00478)    LIM_DOMAIN_2 (PS50023)   
Domains : Interpro (EBI)LPP    Znf_LIM   
Domain families : Pfam (Sanger)LIM (PF00412)   
Domain families : Pfam (NCBI)pfam00412   
Domain families : Smart (EMBL)LIM (SM00132)  
DMDM Disease mutations4026
Blocks (Seattle)LPP
SuperfamilyQ93052
Human Protein AtlasENSG00000145012
Peptide AtlasQ93052
HPRD02828
IPIIPI00023704   IPI00793907   IPI00884332   IPI00797120   IPI00924594   IPI00927909   IPI00927693   IPI00927466   IPI00927168   IPI00794013   IPI00926750   IPI00926532   
Protein Interaction databases
DIP (DOE-UCLA)Q93052
IntAct (EBI)Q93052
FunCoupENSG00000145012
BioGRIDLPP
STRING (EMBL)LPP
ZODIACLPP
Ontologies - Pathways
QuickGOQ93052
Ontology : AmiGOprotein binding  nucleus  cytoplasm  plasma membrane  focal adhesion  cell adhesion  biological_process  zinc ion binding  
Ontology : EGO-EBIprotein binding  nucleus  cytoplasm  plasma membrane  focal adhesion  cell adhesion  biological_process  zinc ion binding  
NDEx NetworkLPP
Atlas of Cancer Signalling NetworkLPP
Wikipedia pathwaysLPP
Orthology - Evolution
OrthoDB4026
GeneTree (enSembl)ENSG00000145012
Phylogenetic Trees/Animal Genes : TreeFamLPP
Homologs : HomoloGeneLPP
Homology/Alignments : Family Browser (UCSC)LPP
Gene fusions - Rearrangements
Fusion : MitelmanFAM19A3/LPP [1p13.2/3q28]  [t(1;3)(p13;q28)]  
Fusion : MitelmanHMGA2/LPP [12q14.3/3q28]  [t(2;12)(q37;q14)]  [t(3;12)(q28;q14)]  
Fusion : MitelmanLPP/ABHD17C [3q28/15q25.1]  [t(3;15)(q28;q25)]  
Fusion : MitelmanLPP/BCL6 [3q28/3q27.3]  [del(3)(q27)]  [del(3)(q27q28)]  
Fusion : MitelmanLPP/CASR [3q28/3q21.1]  [t(3;3)(q21;q28)]  
Fusion : MitelmanLPP/F2 [3q28/11p11.2]  [t(3;11)(q28;p11)]  
Fusion : MitelmanLPP/GOLIM4 [3q28/3q26.2]  [t(3;3)(q26;q28)]  
Fusion : MitelmanLPP/SPATA16 [3q28/3q26.31]  [t(3;3)(q26;q28)]  
Fusion : MitelmanLPP/ST6GAL1 [3q28/3q27.3]  [t(3;3)(q27;q28)]  
Fusion : MitelmanSEPT9/LPP [17q25.2/3q28]  [t(3;17)(q28;q25)]  
Fusion : MitelmanTC2N/LPP [14q32.12/3q28]  [t(3;14)(q28;q32)]  
Fusion : COSMICLPP [3q28]  -  KMT2A [11q23.3]  [fusion_1820]  [fusion_1821]  
Fusion: TCGALPP 3q28 CASR 3q21.1 OV
Fusion: TCGALPP 3q28 CLSTN2 3q23 HNSC
Fusion: TCGALPP 3q28 F2 11p11.2 OV
Fusion: TCGALPP 3q28 FAM108C1 BRCA
Fusion: TCGALPP 3q28 GOLIM4 3q26.2 LUSC
Fusion: TCGALPP 3q28 LEPREL1 HNSC
Fusion: TCGALPP 3q28 SPATA16 3q26.31 BRCA
Fusion: TCGALPP 3q28 ST6GAL1 3q27.3 LUSC
Fusion: TCGALPP 3q28 TP63 3q28 BRCA
Fusion: TCGASEPT9 17q25.2 LPP 3q28 BRCA
Fusion: TCGATC2N 14q32.12 LPP 3q28 LUSC
Fusion : TICdbHMGA2 [12q14.3]  -  LPP [3q28]
Fusion : TICdbKMT2A [11q23.3]  -  LPP [3q28]
Fusion Cancer (Beijing)SFTPB [2p11.2]  -  LPP [3q28]  [FUSC002777]
Polymorphisms : SNP, variants
NCBI Variation ViewerLPP [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)LPP
dbVarLPP
ClinVarLPP
1000_GenomesLPP 
Exome Variant ServerLPP
ExAC (Exome Aggregation Consortium)LPP (select the gene name)
Genetic variants : HAPMAP4026
Genomic Variants (DGV)LPP [DGVbeta]
Mutations
ICGC Data PortalLPP 
TCGA Data PortalLPP 
Broad Tumor PortalLPP
OASIS PortalLPP [ Somatic mutations - Copy number]
Cancer Gene: CensusLPP 
Somatic Mutations in Cancer : COSMICLPP 
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch LPP
DgiDB (Drug Gene Interaction Database)LPP
DoCM (Curated mutations)LPP (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)LPP (select a term)
intoGenLPP
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)3:187943193-188608460  ENSG00000145012
CONAN: Copy Number AnalysisLPP 
Mutations and Diseases : HGMDLPP
OMIM600700   
MedgenLPP
Genetic Testing Registry LPP
NextProtQ93052 [Medical]
TSGene4026
GENETestsLPP
Huge Navigator LPP [HugePedia]
snp3D : Map Gene to Disease4026
BioCentury BCIQLPP
ClinGenLPP
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4026
Chemical/Pharm GKB GenePA30440
Clinical trialLPP
Miscellaneous
canSAR (ICR)LPP (select the gene name)
Probes
Litterature
PubMed75 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineLPP
EVEXLPP
GoPubMedLPP
iHOPLPP
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Sep 28 15:55:53 CEST 2016

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