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NBPF26

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NBPF26
Identifiers
AliasesNBPF26, NBPF member 26
External IDsHomoloGene: 41035; GeneCards: NBPF26; OMA:NBPF26 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

101060684

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Ensembl

ENSG00000273136

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UniProt

n
a

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RefSeq (mRNA)

NM_001351372
NM_001395637
NM_001405520

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RefSeq (protein)

n/a

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Location (UCSC)Chr 1: 120.72 – 120.84 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

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

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Locus

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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

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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

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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

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Composition

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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

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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 Olduvai Domains
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

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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

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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

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Orthologs

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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 Orthologs
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

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Human NBPF26 has multiple paralogs. The top 10 are shown in the table below.

Human NBPF26 Paralogs
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

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NBPF26 RNA expression is ubiquitous throughout human tissue.[20]

Clinical Significance

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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

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A conceptual translation of human NBPF26 is shown below.

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000273136 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ NCBI gene entry for NBPF26
  4. ^ 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.
  5. ^ NCBI gene entry for NBPF26
  6. ^ AlphaFold <https://alphafold.ebi.ac.uk/entry/A0A2J8IZQ5>
  7. ^ Expasy compute pI <https://web.expasy.org/cgi-bin/compute_pi/pi_tool[permanent dead link‍]>
  8. ^ Statistical Analysis of Protein Sequences (SAPS)<https://www.ebi.ac.uk/Tools/seqstats/saps>
  9. ^ MotifFinder <https://www.genome.jp/tools-bin/search_motif_lib>
  10. ^ MyHits Motif Scan <https://myhits.sib.swiss/cgi-bin/motif_scan>
  11. ^ DTU NetPhos <https://services.healthtech.dtu.dk/services/NetPhos-3.1/>
  12. ^ GPS <https://gps.biocuckoo.cn/online.php>
  13. ^ Sulfinator <https://web.expasy.org/sulfinator/>
  14. ^ NetCGlyc <https://services.healthtech.dtu.dk/services/NetCGlyc-1.0/>
  15. ^ NetNGlyc 1.0 < https://services.healthtech.dtu.dk/services/NetNGlyc-1.0/>
  16. ^ NetOGlyc 4.0 <https://services.healthtech.dtu.dk/services/NetOGlyc-4.0/>
  17. ^ ProP 1.0 <https://services.healthtech.dtu.dk/services/ProP-1.0/>
  18. ^ IntAct database <https://www.ebi.ac.uk/intact/home>
  19. ^ BioGrid < https://thebiogrid.org/>
  20. ^ NBPF26 RNA expression <https://www.ncbi.nlm.nih.gov/gene/101060684>
  21. ^ 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
  22. ^ 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
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