NBPF26
| NBPF26 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | NBPF26, NBPF member 26 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | HomoloGene: 41035 GeneCards: NBPF26 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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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[edit]
Locus[edit]
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[edit]
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[edit]
NBPF26 encodes three isoform variants shown in the table below. Isoform one is the longest variant and spans 6,891 base pairs.[5]
| 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[edit]
Composition[edit]
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[edit]
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.
| Clade | Position (aa) | Sequence |
|---|---|---|
| Con1 | 442-505 | EKVLESSAPREVQKTEESKVPEDSLEECAITCSNSHGPCDSNQPHKNIKITFEEDEVNSTLVVD |
| Con1 | 713-775 | EKVQKSSAPREMQKAEEKEVPEDSLEECAITCSNSHGPYDCNQPHRKTKITFEEDKVDSTLIG |
| Con2 | 799-862 | EEKGPVSPRNLQESEEEEVPQESWDEGYSTLSIPPEMLASYKSYSSTFHSLEEQQVCMAVDIG |
| HLS1 | 871-937 | KEDHEATGPRLSRELLDEKGPEVLQDSLDRCYSTPSGCLELTDSCQPYRSAFYVLEQQRVGLAVDMD |
| HLS1 | 946-1,012 | EEDQDPSCPRLSGELLDEKEPEVLQESLDRCYSTPSGCLELTDSCQPYRSAFYILEQQRVGLAVDMD |
| HLS1 | 1,021-1,087 | EEDQDPSCPRLSGELLDEKEPEVLQESLDRCYSTPSGCLELTDSCQPYRSAFYILEQQRVGLAVDMD |
| HLS2 | 1,096-1,162 | EEDQDPSCPRLSRELLDEKEPEVLQDSLGRCYSTPSGYLELPDLGQPYSSAVYSLEEQYLGLALDVD |
| HLS3 | 1,171-1,237 | EEDQGPPCPRLSRELLEVVEPEVLQDSLDRCYSTPSSCLEQPDSCQPYGSSFYALEEKHVGFSLDV |
| HLS1 | 1,265-1331 | EEDQNPPCPRLSRELLDEKGPEVLQDSLDRCYSTPSGCLELTDSCQPYRSAFYILEQQRVGLAVDMD |
| HLS3 | 1,340-1,406 | EEDQDPSCPRLSRELLEVVEPEVLQDSLDRCYSTPSSCLEQPDSCQPYGSSFYALEEKHVGFSLDVG |
| HLS2 | 1,415-1,481 | EEDQDPSCPRLSRELLDEKEPEVLQDSLGRCYSTPSGYLELPDLGQPYSSAVYSLEEQYLGLALDVD |
| HLS3 | 1,490-1,556 | EEDQGPPCPRLSRELLEVVEPEVLQDSLDRCYSTPSSCLEQPDSCQPYGSSFYALEEKHVGFSLDVG |
| Con3 | 1,584-1,650 | EEDQNPPCPRLNSMLMEVEEPEVLQDSLDICYSTPSMYFELPDSFQHYRSVFYSFEEEHISFALYVD |
Post-translational modifications[edit]
NBPF26 is phosphorylated at amino acids 46, 48, 97, and 228.[11][12] In addition, NBPF26 is predicted to undergo sulfonation, C-mannosylation, N-glycosylation, and O-glycosylation.[13][14][15][16] Three furin cleavage sites are found at amino acid positions 379, 1252, and 1571.[17]
Protein interactions[edit]
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[edit]
Orthologs[edit]
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.
| Class | Genus and Species | Common name | Gene name | Accession # | Length (aa) | Identity (%) | Similarity (%) |
|---|---|---|---|---|---|---|---|
| Mammalia | Pan troglodytes | Chimpanzee | NBPF14 | XP_054958524 | 1,615 | 53.9 | 57.8 |
| Mammalia | Gorilla gorilla gorilla | Gorilla | NBPF12 | XP_055212742.1 | 2,428 | 54.3 | 56.0 |
| Mammalia | Mus musculus | House Mouse | NOTCH2 | NP_035058.2 | 2,473 | 16.0 | 21.2 |
| Mammalia | Enhydra lutris kenyoni | Northern Sea Otter | NBPF26 | XP_022351917.1 | 2,358 | 12.3 | 21.6 |
| Aves | Dryobates pubescens | Downy woodpecker | NOTCH2 | XP_054021673.1 | 2,453 | 20.1 | 29.7 |
| Aves | Antrostomus carolinensis | Chuck-will's-widow | NOTCH2 | XP_010174161 | 2,401 | 19.1 | 28.5 |
| Aves | Strigops habroptila | Owl Parrot | NOTCH2 | XP_030350503.1 | 2,432 | 15.6 | 22.4 |
| Aves | Anser cygnoides | Swan goose | NBPF26 | XP_047936201.1 | 2,359 | 13.7 | 24.1 |
| Reptilia | Trachemys scripta elegans | Red-eared slider | NOTCH2 | XP_034634874.1 | 2,397 | 20.0 | 29.8 |
| Reptilia | Alligator mississippiensis | American alligator | NOTCH2 | XP_006260017.1 | 2,435 | 16.7 | 24.2 |
| Reptilia | Podarcis raffonei | Aeolian wall lizard | NOTCH1 | XP_053230981.1 | 2,531 | 14.6 | 22.8 |
| Reptilia | Pseudonaja textilis | Eastern brown snake | NOTCH3 | XP_026552021.1 | 2,416 | 14.3 | 21.3 |
| Amphibia | Spea bombifrons | Plains spadefoot toad | NOTCH2L | XP_053317909.1 | 2,419 | 17.0 | 25.7 |
| Amphibia | Xenopus laevis | African clawed frog | NOTCH2 | XP_018114267.1 | 2,450 | 15.0 | 22.6 |
| Amphibia | Geotrypetes seraphini | Gaboon caecilian | NOTCH3 | XP_033779639.1 | 2,472 | 14.6 | 21.8 |
| Amphibia | Hyla sarda | Sardinian tree frog | MTF1 | XP_056404323.1 | 1,169 | 12.4 | 22.3 |
| Chordata | Acipenser ruthenus | Sterlet | NOTCH2 | XP_058887354.1 | 2,454 | 16.4 | 24.7 |
| Chordata | Callorhinchus milii | Australian ghostshark | NOTCH2 | XP_042190840.1 | 2,819 | 16.0 | 23.8 |
| Chordata | Petromyzon marinus | Sea lamprey | NOTCH1L | XP_032815028.1 | 2,536 | 14.9 | 23.2 |
| Chordata | Paramormyrops kingsleyae | Elephantfish | NOTCH2L | XP_023699719.1 | 2,420 | 14.4 | 22.2 |
| Invertebrates | Amphimedon queenslandica | Sponge | FBPP1L | XP_019855855 | 698 | 8.1 | 14.4 |
Paralogs[edit]
Human NBPF26 has multiple paralogs. The top 10 are shown in the table below.
| Name | Accession # | Length (aa) | Identity (%) | Similarity (%) |
|---|---|---|---|---|
| NBPF1 | NP_001392595.1 | 1,704 | 68.8 | 71.6 |
| NBPF7 | NP_001392671.1 | 1,704 | 68.2 | 71.0 |
| LOC102724250 | NP_001392459.1 | 1,704 | 67.7 | 70.4 |
| NBPF1L | NP_001393481.1 | 1,949 | 66.1 | 68.7 |
| NBPF12 | KAI4082365.1 | 1,459 | 65.1 | 67.3 |
| NBPF9 | NP_001264373.1 | 1,111 | 64.7 | 65.2 |
| NBPF20 | XP_047301971.1 | 1,065 | 61.7 | 62.5 |
| KIAA1693 | BAB21784.1 | 901 | 50.7 | 51.8 |
| NBPF8 | XP_047285792.1 | 1,353 | 48.6 | 50.0 |
| NBPF11 | NP_001095133.3 | 865 | 46.3 | 47.9 |
Expression[edit]
NBPF26 RNA expression is ubiquitous throughout human tissue.[20]
Clinical Significance[edit]
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[edit]
A conceptual translation of human NBPF26 is shown below.
References[edit]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000273136 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ NCBI gene entry for NBPF26
- ^ 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.
- ^ NCBI gene entry for NBPF26
- ^ AlphaFold <https://alphafold.ebi.ac.uk/entry/A0A2J8IZQ5>
- ^ Expasy compute pI <https://web.expasy.org/cgi-bin/compute_pi/pi_tool[permanent dead link]>
- ^ Statistical Analysis of Protein Sequences (SAPS)<https://www.ebi.ac.uk/Tools/seqstats/saps>
- ^ MotifFinder <https://www.genome.jp/tools-bin/search_motif_lib>
- ^ MyHits Motif Scan <https://myhits.sib.swiss/cgi-bin/motif_scan>
- ^ DTU NetPhos <https://services.healthtech.dtu.dk/services/NetPhos-3.1/>
- ^ GPS <https://gps.biocuckoo.cn/online.php>
- ^ Sulfinator <https://web.expasy.org/sulfinator/>
- ^ NetCGlyc <https://services.healthtech.dtu.dk/services/NetCGlyc-1.0/>
- ^ NetNGlyc 1.0 < https://services.healthtech.dtu.dk/services/NetNGlyc-1.0/>
- ^ NetOGlyc 4.0 <https://services.healthtech.dtu.dk/services/NetOGlyc-4.0/>
- ^ ProP 1.0 <https://services.healthtech.dtu.dk/services/ProP-1.0/>
- ^ IntAct database <https://www.ebi.ac.uk/intact/home>
- ^ BioGrid < https://thebiogrid.org/>
- ^ NBPF26 RNA expression <https://www.ncbi.nlm.nih.gov/gene/101060684>
- ^ 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