LPP (lipoma preferred partner)

2004-05-01   Marleen M Petit 

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

Identity

HGNC
LOCATION
3q28
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
-
FUSION GENES

DNA/RNA

Atlas Image

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

Proteins

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

Entity name
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 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.
Fusion 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.
Atlas Image
Entity name
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 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.
Fusion 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 name
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 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.
Fusion 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 name
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 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.
Fusion 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 name
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 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.
Fusion 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

Atlas Image

Bibliography

Pubmed IDLast YearTitleAuthors
114335292001Human LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23).Dahéron L et al
146140532003Fusion, disruption, and expression of HMGA2 in bone and soft tissue chondromas.Dahlén A et al
127609072003LPP, a LIM protein highly expressed in smooth muscle.Gorenne I et al
120633922001A novel LPP fusion gene indicates the crucial role of truncated LPP proteins in lipomas and pulmonary chondroid hamartomas.Lemke I et al
126159772003The lipoma preferred partner LPP interacts with alpha-actinin.Li B et al
128695772003Prediction of cell type-specific gene modules: identification and initial characterization of a core set of smooth muscle-specific genes.Nelander S et al
106372952000LPP, an actin cytoskeleton protein related to zyxin, harbors a nuclear export signal and transcriptional activation capacity.Petit MM et al
124413562003The focal adhesion and nuclear targeting capacity of the LIM-containing lipoma-preferred partner (LPP) protein.Petit MM et al
88124231996LPP, the preferred fusion partner gene of HMGIC in lipomas, is a novel member of the LIM protein gene family.Petit MM et al
97729041998Expression of reciprocal fusion transcripts of the HMGIC and LPP genes in parosteal lipoma.Petit MM et al
95987961998The t(3;12)(q27;q14-q15) with underlying HMGIC-LPP fusion is not determining an adipocytic phenotype.Rogalla P et al

Other Information

Locus ID:

NCBI: 4026
MIM: 600700
HGNC: 6679
Ensembl: ENSG00000145012

Variants:

dbSNP: 4026
ClinVar: 4026
TCGA: ENSG00000145012
COSMIC: LPP

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000145012ENST00000414139C9J1K7
ENSG00000145012ENST00000415906C9JXK9
ENSG00000145012ENST00000416784C9J4E3
ENSG00000145012ENST00000420410C9J5C8
ENSG00000145012ENST00000426274C9J3U9
ENSG00000145012ENST00000430340C9J2R5
ENSG00000145012ENST00000443217C9JE51
ENSG00000145012ENST00000448637C9JUT4
ENSG00000145012ENST00000454789C9JT42
ENSG00000145012ENST00000457242C9JIY7
ENSG00000145012ENST00000617246Q93052
ENSG00000145012ENST00000618621A0A087WZF1
ENSG00000145012ENST00000640853Q93052

Expression (GTEx)

0
50
100
150
200

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
190739672008Shared and distinct genetic variants in type 1 diabetes and celiac disease.249
204105012010Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo.102
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
252799862014Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.39
124413562003The focal adhesion and nuclear targeting capacity of the LIM-containing lipoma-preferred partner (LPP) protein.32
167383192006The LIM domain protein LPP is a coactivator for the ETS domain transcription factor PEA3.31
173221712007Angiotensin II, focal adhesion kinase, and PRX1 enhance smooth muscle expression of lipoma preferred partner and its newly identified binding partner palladin to promote cell migration.26
197014942009Cell Adhesion and Transcriptional Activity - Defining the Role of the Novel Protooncogene LPP.25
156493182005The tumor suppressor Scrib interacts with the zyxin-related protein LPP, which shuttles between cell adhesion sites and the nucleus.22

Citation

Marleen M Petit

LPP (lipoma preferred partner)

Atlas Genet Cytogenet Oncol Haematol. 2004-05-01

Online version: http://atlasgeneticsoncology.org/gene/72/lpp