PDZ AND LIM DOMAIN PROTEIN 7; PDLIM7

Alternative titles; symbols

• LIM DOMAIN PROTEIN ENIGMA; ENIGMA
• LIM MINERALIZATION PROTEIN 1; LMP1

HGNC Approved Gene Symbol: PDLIM7

Cytogenetic location: 5q35.3 Genomic coordinates (GRCh38): 5:177,483,393-177,497,603 (from NCBI)

▼ Description
LIM domains, which were named after the worm proteins (Lin11 and Mec3) and vertebrate protein (ISL1; 600366) in which they were first discovered, are cysteine-rich double zinc fingers involved in protein-protein interactions. LIM domain-containing proteins, such as PDLIM7, are scaffolds for the formation of multiprotein complexes. These proteins are involved in cytoskeleton organization, cell lineage specification, organ development, and oncogenesis (Bach, 2000).

▼ Cloning and Expression
Using a yeast 2-hybrid screen of a HeLa cell cDNA library with exon 16 of the insulin receptor (INSR; 147670) as bait, followed by screening a human neuroblastoma cell line, Wu and Gill (1994) isolated a cDNA encoding ENIGMA. The authors designated the protein ENIGMA, in reference to the Allies' deciphering of German messages enciphered on Enigma machines in World War II, based on its endocytic code recognition properties. Sequence analysis predicted that the 455-amino acid protein contains 2 C-terminal LIM domains. Northern blot analysis revealed expression of a 1.7-kb transcript in cell lines. Western blot analysis showed expression of a 55-kD protein, as expected from the primary sequence.

By PCR of osteoblast cell line total RNA using primers designed from rat Lmp1, followed by screening and 5-prime RACE of a heart cDNA library, Liu et al. (2002) cloned LMP1. The deduced 457-amino acid protein has an N-terminal PDZ domain, followed by a unique sequence, a LIM-like motif, and 2 C-terminal LIM domains. Liu et al. (2002) also identified 2 splice variants, which they called LMP2 and LMP3. The LMP2 variant encodes a deduced 423-amino acid protein that retains the PDZ and LIM domains but has an altered unique region. The LMP3 variant encodes a deduced 153-amino acid protein truncated after about 30% of the unique region. PCR detected expression of 1 or more of the variants in all tissues examined. Full-length LMP1 predominated in leukocytes, spleen, lung, placenta, and fetal liver, whereas LMP2 predominated in skeletal muscle, bone marrow, and heart. In tissues were it was detected, LMP3 was a minor transcript.

▼ Gene Function
Yeast 2-hybrid analysis by Wu and Gill (1994) indicated that the complete LIM2 domain of ENIGMA, but not the LIM1 domain, interacts specifically with endocytic codes of INSR, but not with those of IGF1R (147370), LDLR (606945), TFRC (190010), or EGFR (131550). Wu and Gill (1994) suggested that LIM domains provide the structural basis for recognition of tyrosine-containing tight-turn structures.

Using a yeast 2-hybrid analysis, Kuroda et al. (1996) showed that the LIM domains of rat Enh (605904) and human ENIGMA associate with varying protein kinase C (see 176982) isoforms.

Using immunofluorescent and confocal microscopy, Durick et al. (1998) demonstrated that ENIGMA is localized through its PDZ domain to the cell periphery and in some cytoskeletal components, and that ENIGMA colocalizes with RET/PTC2 (188830). Yeast 2-hybrid analysis showed that ENIGMA binds through its LIM2 domain to RET/PTC2 at tyr586 in a phosphorylation-independent manner, and that this interaction, as well as binding by SHC1 (600560), is required for RET/PTC2 mitogenic activity.

Using GST pull-down and immunoprecipitation analyses, Guy et al. (1999) showed that the ENIGMA PDZ domain binds to C-terminal sequences of skeletal beta-tropomyosin (TPM2; 190990), a component of actin filaments. Immunofluorescence and immunoelectron microscopy demonstrated that ENIGMA and TPM2 colocalize at the Z line of the sarcomere and at the boundary of the Z line and the I band. Guy et al. (1999) proposed that ENIGMA is likely to be an adaptor protein that localizes LIM-binding proteins to actin filaments through its PDZ domain.

Liu et al. (2002) demonstrated that transfected full-length LMP1 induced bone nodule formation in rat calvarial osteoblasts (ROB). Following transplantation of LMP1-transfected cells at subcutaneous sites in athymic rats, LMP1 induced bone trabeculae lined with osteoblasts. Conditioned media from transfected ROB cultures also induced bone nodules in fresh ROB cultures. Overexpression of the LMP3 variant was equally active in inducing nodules in ROB cultures. LMP2 did not induce nodule formation in this assay and instead inhibited glucocorticoid-stimulated nodule formation.

Minamide et al. (2003) infected human lung carcinoma cells with adenovirus carrying human LMP1 cDNA (AdLMP1). The infected cells expressed elevated levels of bone morphogenetic protein-2 (BMP2; 112261), BMP4 (112262), BMP6 (112266), BMP7 (112267), and transforming growth factor-beta-1 (TGFB1; 190180). Human buffy coat cells infected with AdLMP1 also demonstrated increased levels of BMP4 and BMP7 protein 72 hours after ectopic implantation in athymic rats, confirming the in vitro hypothesis.

▼ Gene Structure
Liu et al. (2002) determined that the PDLIM7 gene contains 13 exons and spans about 24 kb.

▼ Mapping
By genomic sequence analysis, Liu et al. (2002) mapped the PDLIM7 gene to chromosome 5.