NBPF26, or Neuroblastoma breakpoint family member 26, is a protein encoded by the NBPF26 gene in Homo sapiens. The alias for NBPF26 is notch 2 N-terminal like R (NOTCH2NLR).[3] NBPF26 encodes 13 Olduvai domains, which are thought to contribute to the rapid expansion of the neocortex in humans.[4]
Gene
Locus
The NBPF26 gene is located on the plus strand of chromosome 1 (1p11.2) from 120,723,945 to 120,842,229, spanning 118,285 base pairs. NOTCH2NLR is an alias of NBPF26 and overlaps with beginning of NBPF26's coding sequence.
Genomic neighborhood
Human NBPF26 genomic neighborhood and location.
Within the genomic neighborhood of human NBPF26, phosphodiesterase 4D interacting protein-like pseudogene 2 (PDE4DIPP2), NOTCH2NLR, Rosellinia necatrix victorivirus 1-19 (RnVV1-19), and tRNA-Asn (anticodon GTT) 7-1 (TRN-GTT7-1) can be found.
mRNA
NBPF26 encodes three isoform variants shown in the table below. Isoform one is the longest variant and spans 6,891 base pairs.[5]
Human NBPF26 Isoforms
Isoform
Nucleotide Accession #
mRNA Length (bp)
Protein Accession #
Protein Length (aa)
Molecular Weight (kDa)
1
NM_001405520.1
6,891
NP_001392449.1
1,673
190
2
NM_001351372.2
6,666
NP_001338301.2
1,598
182
3
NM_001395637.2
6,216
NP_001382566.1
1448
165
Protein
Composition
NBPF26 Tertiary Structure. Structure created with AlphaFold.[6]
NBPF26 isoform one has a predicted molecular weight of 190 kDa and an isoelectric point of 4.6.[7] Relative to other proteins, NBPF26 is rich in glutamic acid, glutamine, and cysteine, and poor in isoleucine.[8] Two positive charge clusters, spanning 22 amino acids, are located at positions 1,241-1,262 and 1,560-1,581.
Motifs
Five EGF-like domains and one calcium-binding EGF-like domain are encoded in NBPF26.[9]
NBPF26 also encodes 13 Olduvai domains.[10] Positions and sequences of Conserved 1-3 (Con1-3) and Human lineage-specific 1-3 (HLS1-3) Olduvai clades are shown in the table below.
NBPF26 is predicted to interact with Estrogen receptor 1 (ESR1), APEX nuclease (multifunctional DNA repair enzyme) 1 (APEX1), lysine (K)-specific demethylase 1A (KDM1A), trans-golgi network protein 2 (TGOLN2), and tripartite motif containing 25 (TRIM25).[18][19]
Homology
Orthologs
Distant orthologs for human NBPF26 can be found in primates, birds, reptiles, amphibians, fish, and some invertebrates. Select orthologs are shown in the table below.
NBPF26 RNA expression is ubiquitous throughout human tissue.[20]
Clinical Significance
In lung cancer, mutations in NBPF26 were associated with local disease recurrence.[21] NBPF26 expression in monocytes was increased in pregnant patients with rheumatoid arthritis compared to pregnancies without rheumatoid arthritis.[22]
Conceptual translation
A conceptual translation of human NBPF26 is shown below.
^Fiddes, I. T., Pollen, A. A., Davis, J. M., & Sikela, J. M. (2019). Paired involvement of human-specific Olduvai domains and NOTCH2NL genes in human brain evolution. Human genetics, 138, 715-721.
^Valter, A., Luhari, L., Pisarev, H., Truumees, B., Planken, A., Smolander, O. P., & Oselin, K. (2023). Genomic alterations as independent prognostic factors to predict the type of lung cancer recurrence. Gene, 885, 147690. https://doi.org/10.1016/j.gene.2023.147690
^Lien, H. J. T., Pedersen, T. T., Jakobsen, B., Flatberg, A., Chawla, K., Sætrom, P., & Fenstad, M. H. (2023). Single-cell resolution of longitudinal blood transcriptome profiles in rheumatoid arthritis, systemic lupus erythematosus and healthy control pregnancies. Annals of the rheumatic diseases, ard-2023-224644. Advance online publication. https://doi.org/10.1136/ard-2023-224644
