NBPF3

Neuroblastoma breakpoint family, member 3
Identifiers
Symbols	NBPF3; AE2; DKFZp434D177
External IDs	OMIM: 612992 HomoloGene: 88936 GeneCards: NBPF3 Gene
Gene Ontology Cellular component • cytoplasm Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	84224	n/a
Ensembl	ENSG00000142794	n/a
UniProt	B3KTI0	n/a
RefSeq (mRNA)	XM_001129803	n/a
RefSeq (protein)	XP_001129803	n/a
Location (UCSC)	Chr 1: 21.77 – 21.81 Mb	n/a
PubMed search	[1]	n/a

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.^[1]

Protein Sequence

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.

Isoforms and Sequence Characteristics

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 ^[2]:

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.

Function

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 ^[3].

Homology

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	NPBF3	CAB66824	100%	100%	633
Homo sapiens	NPBF10	NP_001034792.2	77%	83%	867
Homo sapiens	NPBF1	NP_060410.2	75%	83%	1214
Homo sapiens	NPBF20	NP_001032764.1	75%	84%	942
Homo sapiens	NPBF8	XP_001726998.1	75%	84%	3815
Homo sapiens	NPBF16	NP_001096133.1	75%	84%	670
Homo sapiens	NPBF15	NP_775909.1	75%	84%	670
Homo sapiens	NPBF11	NP_899228.3	75%	83%	790
Homo sapiens	NPBF14	NP_056198.1	74%	83%	921
Homo sapiens	NPBF9	XP_001717450.1	80%	88%	687
Homo sapiens	NPBF7	NP_001041445.1	69%	79%	421
Homo sapiens	NPBF6	NP_001137459.1	54%	68%	667
Homo sapiens	NPBF4	NP_001137461.1	53%	67%	638
Homo sapiens	NPBF12	XP_001715862.1	55%	63%	427
Homo sapiens	NPBF5	XP_001714524.1	60%	73%	428

Both orthologs and paralogs of NPBF3 were found using the databases BLAT.^[4] and BLAST ^[5]

Protein Interactions

NPBF3 interacts with three other proteins: C1orf19, Ankyrin-1 (ANK1) and Ewing Sarcoma Breakpoint region 1 (EWSR1).^[6]. It is not known how these proteins interact or what the product of these interactions may be.

References

1. ^ "Entrez Gene: NBPF3 neuroblastoma breakpoint family, member 3". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=84224. 
2. ^ "UniProt". http://www.uniprot.org. Retrieved 14-May-2009. 
3. ^ Vandepoele K, Van Roy N, Staes K, et al. (2006). "A novel gene family NBPF: intricate structure generated by gene duplications during primate evolution.". Mol. Biol. Evol. 22 (11): 2265–74. doi:10.1093/molbev/msi222. PMID 16079250. 
4. ^ "BLAT Search Genome". http://genome.ucsc.edu/cgi-bin/hgBlat?command=start&org=Human&db=hg18&hgsid=122786349. Retrieved 4-May-2009. 
5. ^ "BLAST". http://blast.ncbi.nlm.nih.gov/Blast.cgi. Retrieved 4-May-2009. 
6. ^ "STRING: Known and Predicted Protein-Protein Interactions". http://string.embl.de/. 

Further reading

• Jöns T, Drenckhahn D (1998). "Anion exchanger 2 (AE2) binds to erythrocyte ankyrin and is colocalized with ankyrin along the basolateral plasma membrane of human gastric parietal cells.". Eur. J. Cell Biol. 75 (3): 232–6. PMID 9587054. 
• Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310948. 
• Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=311072. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
• Petroziello J, Yamane A, Westendorf L, et al. (2004). "Suppression subtractive hybridization and expression profiling identifies a unique set of genes overexpressed in non-small-cell lung cancer.". Oncogene 23 (46): 7734–45. doi:10.1038/sj.onc.1207921. PMID 15334068. 
• Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline.". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528930. 
• Vandepoele K, Van Roy N, Staes K, et al. (2006). "A novel gene family NBPF: intricate structure generated by gene duplications during primate evolution.". Mol. Biol. Evol. 22 (11): 2265–74. doi:10.1093/molbev/msi222. PMID 16079250. 
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network.". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
• Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006.". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1347501. 
• Vandepoele K, van Roy F (2007). "Insertion of an HERV(K) LTR in the intron of NBPF3 is not required for its transcriptional activity.". Virology 362 (1): 1–5. doi:10.1016/j.virol.2007.01.044. PMID 17391723.