Table 1.
Quick facts overview of putative LCN2 receptors in mouse and men*.
| NGALR | LRP2** | MC4R | MC1R | MC3R | |
|---|---|---|---|---|---|
| Alternate names | SLC22A17 (H), 24p3R (M), BOCT (H), BOCT1/BOIT (H), LCN2R (H), NGALR2 (H), NGALR3 (H) | Megalin | Body mass index quantitative trait locus 20 (BMIQ20) (H) | melanocyte-stimulating hormone receptor (MSHR), melanotropin receptor (M, H) | MC3 (M, H), Body mass index quantitative trait locus 9 (BMIQ9) (H), HGMP01A (M) |
| Classification | Transmembrane transporter/signaling receptor | Multi-ligand scavenger receptor | G protein-coupled, seven-transmembrane receptors | ||
| Discovery | Murine NGALR was identified as a receptor for LCN2 after three rounds of expression cloning in COS-7 cells using a cDNA library prepared from murine FL5.12 cells (13) | LRP2 was first identified in rats by screening a rat kidney λgt 11 cDNA expression library with antiserum raised against large, negatively charged antigens isolated from rat glomeruli. The initially isolated cDNA clone (C1B) was then used as a probe to isolate longer λgt 11 cDNA clones. Subsequently, a 15.4 kb cDNA encoding an open reading frame of 4660 amino acids was assembled by several rounds of screening of a random-primed rat kidney λZAP II cDNA library (35). | MCR4 was first isolated from a human genomic EMBL3 phage library that was probed with a fragment derived from a PCR amplified from mouse DNA using primers derived from conserved sequences located in the second intracytoplasmic loop and the seventh transmembrane domain of other members of the melanocortin receptor family (36). | Human and mouse MC1Rs were first isolated from melanoma cells (37, 38). | Human MC3R was first cloned from a human EMBL3 phage library using probes derived from PCRs conducted with primers located in the second intracytoplasmic loop and the seventh transmembrane region (39). Mouse MC3R was later isolated from a mouse genomic DNA library screened with a fragment derived from a PCR amplified with degenerative primers corresponding to consensus sequences of the third and sixth transmembrane segments (40). |
| Chromsosomal localization* | H: 14q11.2, M: 14C3 | H: 2q31.1, M: 2C2 | H: 18q21.32, M: 18E1 | H: 16q24.3, M: 8E1 | H: 20q13.2, M: 2H3 |
| Gene structure* | 10 exons | 81 exons (H), 79 (M) | 1 exon | 1 exon | 1 exon |
| mRNA transcript sizes* | H: 4 transcripts (2,426 nt, 2,372 nt, 2,037 nt, 2,037 nt) M: 5 transcripts (6362 nt, 6329 nt, 6225 nt, 2399 nt, 2294 nt) |
H: 7 transcripts (15,657 nt, 15,591 nt, 15,815 nt, 15,531 nt 15,528 nt, 13,251 nt 13,248 nt) M: 15,429 nt |
H: 1714 nt M: 2783 nt |
H: 2,111 nt M: 3,670 nt |
H: 1,084 nt, M: 2,623 nt |
| Protein domains | Signal peptide, major facilitator superfamily (MFS) domain (acting as single-polypeptide secondary carriers capable only of transporting small solutes in response to chemiosmotic ion gradients) | Signal peptide, 36 LDL-receptor class A (LDLRA) domain profiles, 35 LDL-receptor class (LDLRB) repeat profiles, 6 EGF-like domain profiles | G-protein coupled receptors family 1 signature with seven transmembrane regions | ||
| Protein sizes* | H: 649 aa, 631 aa, 302 aa M: 520 aa, 401 aa |
H: 4,655 aa, 4,612 aa, 4,347 aa, 3,892 aa M: 4660 aa, |
H: 332 aa M: 332 aa |
H: 317 aa M: 315 aa |
H: 323 aa M: 323 aa |
| Dissociation constant (K d) for LCN2 binding | ~ 92 pM (41) 7-10 µM (apo-LCN2 to NGALR aa1-aa105) and ~20 µM (LCN2/ferric-enterobactin to NGALRaa1-aa105) (30) |
~ 60 nM (42) | 51.39 ± 4.78 nM (43) | 86.96 ± 9.72 nM (43) | 82.13 ± 12.14 nM (43) |
| Animal models | Homozygote mutant mice are embryonic lethal [personal communication Yukio Nakamura, RIKEN BioResource Research Center]. | Homozygote Lrp2 mutant mice usually die perinatally from respiratory insufficiency within the first few minutes after birth or within 2-3 hours (44). However, there are also reports showing that Lrp2 deficient mice can survive at low frequency (45). | Mice deficient for Mc4r develop a maturity-onset obesity syndrome associated with hyperphagia, hyperinsulinemia, and hyperglycemia (46). | The lack of Mc1r in mice results in a yellow coat in mice (47). | Mcr3 deficient mice have increased fat mass, reduced lean mass and higher feed efficiency than wild type mice (48). |
* Data was taken from different databases (OMIM, Gene, Genome) hosted by the National Library of Medicine (https://www.ncbi.nlm.nih.gov/). ** Recently, mouse LRP6 was shown to bind mouse LCN2 in co-immunoprecipitation assay (49). Abbreviations used are: aa, amino acids; H, human; M, mouse.