Neuroblastoma breakpoint family, member 3, also known as NBPF3, is a human gene of the neuroblastoma breakpoint family, which resides on chromosome 1 of the human genome. NBPF3 is located at 1p36.12, immediately upstream of genes ALPL and RAP1GAP. [3]
The NBPF3 gene is 633 amino acids long and contains five DUF1220 domains, which are highlighted in the image below. DUF1220 domains are found in all other members of the neuroblastoma breakpoint family. The protein has a very repetitive structure, since, along with the remaining members of its protein family, it likely arose form segmental duplications on chromosome 1.
The domains are located at residues 236–298, 322–385, 394–460, 469–535, and 544–610.
The protein sequence is rich in three amino acids that are polar and negatively charged at physiological pH: glutamic acid, aspartic acid and glutamine. The isoelectric point of the protein is 4.21, the acidity of which may be attributed to the abundance of these amino acids.
There are four known isoforms of the NPBF3 gene. While isoform 1 is the dominant form of the gene, each other isoform has unique changes to the protein sequence that may affect the structure, expression or function of the gene product: [4]
| Isoform | Sequence Omissions | Sequence Additions | Length |
| 1 | - | - | 633 |
| 2 | 1-56 | - | 577 |
| 3 | 350-386 | 331 R→RSSGRFCCLISVGYIFCHPCPAWLIR | 621 |
| 4 | 1-358 | - | 275 |
These isoforms are represented in the following schematic, along with additional sequence characteristics which include Poly-Glu compositional biases and a potential coiled coil.
The function of the neuroblastoma breakpoint family proteins, including NPBF3, is not yet understood by the scientific community. Because of the repetitive composition of this family of genes as well as their amplification in primates, it has been suggested that the family is involved in cognitive development and the evolution of primates.
It has also been suggested that there is a connection between the neuroblastoma breakpoint family and oncogenesis. Due to the up-regulation of NBPF genes in some tumor tissues, proteins of this family have been hypothesized to be oncogenes. It has also been suggested that members of the neuroblastoma breakpoint family are tumor suppressor genes, due to a loss of heterozygosity in tumor tissue in the region of chromosome 1 where NBPF3 and other NBPF proteins are located. [5]
Orthologs of NBPF3 are found primarily in primate species, though orthologous sequences can be found in cow, horse, and dog species. There is no mouse ortholog of NPBF3.
| Species | Organism common name | NCBI accession | Sequence identity | Sequence similarity | Length (AAs) | Number of DUF1220 domains |
| Homo sapiens | Human | CAB66824 | 100% | 100% | 633 | 5 |
| Pan troglodytes | Chimpanzee | XP_001163311.1 | 96% | 98% | 633 | 5 |
| Macaca mulatta | Rhesus macaque | XP_001114167.1 | 55% | 65% | 620 | 4 |
| Pongo albelii | Orangutan | NP_001127345.1 | 89% | 93% | 202 | 3 |
| Bos taurus | Cow | XP_611707.4 | 33% | 49% | 816 | 4 |
| Equus caballus | Horse | XP_001916030.1 | 37% | 55% | 1037 | 0 |
| Canis lupus familiaris | Dog | XP_540269.2 | 40% | 59% | 176 | 0 |
NPBF3 has many human paralogs because it is a member of a gene family.
| Species | Gene name | NCBI accession | Sequence identity | Sequence similarity | Length (AAs) |
| Homo sapiens | NBPF3 | CAB66824 | 100% | 100% | 633 |
| Homo sapiens | NBPF10 | NP_001034792.2 | 77% | 83% | 867 |
| Homo sapiens | NBPF1 | NP_060410.2 | 75% | 83% | 1214 |
| Homo sapiens | NBPF20 | NP_001032764.1 | 75% | 84% | 942 |
| Homo sapiens | NBPF8 | XP_001726998.1 | 75% | 84% | 3815 |
| Homo sapiens | NBPF16 | NP_001096133.1 | 75% | 84% | 670 |
| Homo sapiens | NBPF15 | NP_775909.1 | 75% | 84% | 670 |
| Homo sapiens | NBPF11 | NP_899228.3 | 75% | 83% | 790 |
| Homo sapiens | NBPF14 | NP_056198.1 | 74% | 83% | 921 |
| Homo sapiens | NBPF9 | XP_001717450.1 | 80% | 88% | 687 |
| Homo sapiens | NBPF7 | NP_001041445.1 | 69% | 79% | 421 |
| Homo sapiens | NBPF6 | NP_001137459.1 | 54% | 68% | 667 |
| Homo sapiens | NBPF4 | NP_001137461.1 | 53% | 67% | 638 |
| Homo sapiens | NBPF12 | XP_001715862.1 | 55% | 63% | 427 |
| Homo sapiens | NBPF5 | XP_001714524.1 | 60% | 73% | 428 |
Both orthologs and paralogs of NBPF3 were found using the databases BLAT. [6] and BLAST [7]
NPBF3 interacts with three other proteins: C1orf19, ankyrin-1 (ANK1) and Ewing sarcoma breakpoint region 1 (EWSR1). [8] It is not known how these proteins interact or what the product of these interactions may be.
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speciation event (orthologs), or a duplication event (paralogs), or else a horizontal gene transfer event (xenologs).
Protein SSX2 is a protein that in humans is encoded by the SSX2 gene.
Nesprin-2 is a protein that in humans is encoded by the SYNE2 gene. The human SYNE2 gene consists of 116 exons and encodes nesprin-2, a member of the nuclear envelope (NE) spectrin-repeat (nesprin) family. Nesprins are modular proteins with a central extended spectrin-repeat (SR) rod domain and a C-terminal Klarsicht/ANC-1/Syne homology (KASH) transmembrane domain, which acts as a NE-targeting motif. Nesprin-2 (Nesp2) binds to cytoplasmic F-actin, tethering the nucleus to the cytoskeleton and maintaining the structural integrity of the nucleus.
WD repeat and SOCS box-containing protein 1 is a protein that in humans is encoded by the WSB1 gene.
Dimethylaniline monooxygenase [N-oxide-forming] 2 is an enzyme that in humans is encoded by the FMO2 gene.
Ankyrin repeat and SOCS box protein 2 is a protein that in humans is encoded by the ASB2 gene.
Pogo transposable element with ZNF domain is a protein that in humans is encoded by the POGZ gene.
Ankyrin repeat domain-containing protein 17 is a protein that in humans is encoded by the ANKRD17 gene.
Leucine-rich repeat neuronal protein 1 is a protein that in humans is encoded by the LRRN1 gene.
KN motif and ankyrin repeat domain-containing protein 1 is a protein that in humans is encoded by the KANK1 gene.
Myomegalin, also known as phosphodiesterase 4D-interacting protein or cardiomyopathy-associated protein 2, is a protein that in humans is encoded by the PDE4DIP gene. It has roles in the formation of microtubules from the centrosome. Its name derives from the fact that it is highly expressed in units of tubular myofibrils known as sarcomeres and is a large protein, at 2,324 amino acids. It was first characterised in 2000.
Ankyrin 1, also known as ANK-1, and erythrocyte ankyrin, is a protein that in humans is encoded by the ANK1 gene.
Ankyrin repeat and SOCS box protein 1 is a protein that is in humans, encoded by the ASB1 gene.
Ankyrin repeat and BTB/POZ domain-containing protein 1 is a protein that in humans is encoded by the ABTB1 gene.
Neuroblastoma breakpoint family, member 15, also known as NBPF15, is a protein which in humans is encoded by the NBPF15 gene. The gene is 18762 bp long, with mRNA that is 3837 bp long. The gene is located on chromosome 1q21.1. Its sub-cellular location is predicted to be in the nucleus and cytoplasm. It contains what is known as the NBPF repeat, which is a two-exon stretch of sequence that is characteristic of all 21 members of the NBPF gene family. The repeat is considered the ancestral exons, and the NBPF family has been linked to primate evolution.
Neuroblastoma breakpoint family member 10 is a protein that in Homo sapiens is encoded by the NBPF10 gene.
Chromosome X open reading frame 36 (CXorf36) is a gene that in humans encodes a protein “hypothetical protein LOC79742”. This protein has a function that is not currently very well understood. Other known aliases are “FLJ14103, DKFZp313K0825, FLJ55198, PRO3743, FLJ55198, hCG1981635, bA435K1.1,” and “4930578C19Rik.”
Neuroblastoma breakpoint family, member 1, or NBPF1, is a protein that is encoded by the gene NBPF1 in humans. This protein is member of the neuroblastoma breakpoint family of proteins, a group of proteins that are thought to be involved in the development of the nervous system.
Neuroblastoma breakpoint family member 19, or NBPF19, is a protein that in humans is encoded by the NBPF19 gene. This protein is included in the neuroblastoma breakpoint family of proteins.
The neuroblastoma breaking point family (NBPF) is a family of genes involved in neuronal development. The family is highly specific to primates, with minimal similarity or presence in other mammals and no presence in other animals, and its genes' content has been subject to a very high number of duplications in humans. It was described by Vandepoele et al. in 2005 and named as such because NBPF1 was found to be broken by a chromosomal translocation in a neuroblastoma patient.
