LRP1B belongs to the low density lipoprotein (LDL) receptor gene family. These receptors play a wide variety of roles in normal cell function and development due to their interactions with multiple ligands (Liu et al., 2001).

By analyzing a region of chromosome 2 deleted in kidney and bladder cancer cell lines, followed by 5-prime and 3-prime RACE of fetal and adult kidney, fetal brain, and adult lung cDNA, Liu et al. (2000) cloned LRP1B, which they designated LRPDIT. The deduced protein contains 4,599 amino acids and has a calculated molecular mass of about 500 kD. LRP1B has multiple copies of structural motifs conserved in other members of the LDL receptor family. The extracellular N terminus contains 32 cysteine-rich ligand-binding domains, 8 EGF precursor (131530)-like domains, which are required for release of the bound ligands in the endosome, and a cassette of 6 single EGF-like domains near the transmembrane domain. The short cytoplasmic C terminus contains 2 conserved NPxY internalization motifs. LRP1B shares 59% amino acid identity with LRP1 (107770), and their domain structures are nearly identical. RT-PCR and Northern blot analyses detected LRP1B expression in fetal and adult kidney, brain, lung, heart, and liver. EST database analysis indicated that LRP1B is also expressed in skeletal muscle and thyroid gland, as well as in brain lesions of patients with multiple sclerosis (126200).

Using RNA dot blot analysis, Liu et al. (2001) detected LRP1B expression in all regions of the adult brain examined. Thyroid gland, salivary gland, and fetal brain also expressed LRP1B, but heart, liver, kidney, lung, and placenta did not.

By RT-PCR, Marschang et al. (2004) found that full-length mouse Lrp1b was expressed predominantly in brain, while an alternatively spliced form lacking exon 90 was expressed preferentially in adrenal gland and testis. Despite the presence of a potential furin (136950) cleavage site in Lrp1b, Western blot analysis of crude membrane preparations of several mouse tissues identified a single 600-kD protein expressed only in brain.

Liu et al. (2001) found that full-length LRP1B was unstable following transfection in Lrp1 null Chinese hamster ovary (CHO) cells. In order to characterize the ligands for LRP1B, Liu et al. (2001) generated a minireceptor of LRP1B that could be stably expressed in CHO cells. The minireceptor began with the EGF precursor-like repeat before the fourth cluster of ligand-binding repeats (domain IV) and contained ligand-binding domain IV, the transmembrane domain, and the cytoplasmic tail. Ligands for the minireceptor, including receptor-associated protein (104225), urokinase plasminogen activator (191840), tissue-type plasminogen activator (173370), and plasminogen activator inhibitor-1 (173360), were bound, internalized, and degraded via their association with the minireceptor. Kinetic analysis showed that LRP1B was slower in ligand internalization than LRP1.

Liu et al. (2000) determined that the LRP1B gene contains 91 exons and spans more than 500 kb. The sizes and location of exons are similar in LRP1B and LRP1.

Liu et al. (2000) mapped the LRP1B gene to chromosome 2q21.2, a region deleted in some aggressive cancers.

Liu et al. (2000) found that LRP1B was homozygously deleted in 17% (14 of 23) of nonsmall cell lung cancer (NSCLC) cell lines. Expression of only abnormal transcripts missing portions of the LRP1B sequence was found in an additional 30% (11 of 36) of NSCLC cell lines. A missense mutation at codon 3157 was detected in 1 of 4 NSCLC cell lines. In contrast, no LRP1B alterations were identified in a major fraction of SCLC lines, indicating that LRP1B is preferentially inactivated in 1 histologic type of lung cancer.

Marschang et al. (2004) found that Lrp1b-deficient mice appeared normal, were fertile, and produced normal litter sizes. No abnormalities were observed over their life spans, with the oldest animals close to 2 years of age. Lrp1b deficiency had no effects on electrophysiologic measures of brain function.