Biology:BTBD16

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BTB Domain-containing 16 (BTBD16) is a protein which in humans is encoded by the BTBD16 gene. The primary alias is chromosome 10 open reading frame 87 (c10orf87), but this is less commonly used than BTBD16.

Gene

In the human genome, BTBD16 is located on the plus strand of chromosome 10 at 10q26.13.[1] The sequence spans 66,682 base pairs and contains 16 exons.[2] There are two main regions within the BTBD16 protein: the Broad-Complex, Tramtrack, and Bric a brac (BTB) and poxvirus and zinc finger (POZ) domain (BTB/POZ) and the BTB and C-terminal Kelch (BACK) domain.

Expression

BTBD16 is expressed at low levels across all tissues in the human body. Highest expression is within the brain, spinal cord, and liver, though these are each still expressed below the 50th percentile compared to other human proteins.[3] There is also marginally higher expression within the urinary bladder and testes at 4.5 RPKM and 2.5 RPKM, respectively, though at lower confidence.[4]

mRNA

There are 7 known splice variants in humans, with transcript variant 1 having the longest nucleotide length at 1859 nucleotides and encoding the longest isoform, protein isoform A, at 507 amino acids.[5]

Homo sapiens BTBD16 Transcript Variants and Protein Isoforms
Transcript Variant Accession # Nucleotide Length Protein Isoform Accession # Amino Acid Length
1 NM_001318189.3 1859 a NP_001305118.1 507
2 NM_144587.5 1856 b NP_653188.2 506
X1 XM_011539239.3 1739 X1 XP_011537541.1 467
X2 XM_011539240.3 1715 X2 XP_011537542.1 459
X3 XM_011539241.3 1658 X3 XP_011537543.1 440
X4 XM_011539242.3 1538 X4 XP_011537544.1 400
X5 XM_017015637.2 2563 X5 XP_016871126.1 338

Regulation

There are few noted regulation sites within transcript variant 1:[6]

  • upstream in-frame stop codon ("taa" at location 244–246)
  • poly-A signal sequence ("aataaa" at location 1839–1844)
  • poly-A site ("a" at location 1859)
Homo sapiens BTBD16 5' UTR Predicted Structure.[7] Green arrows point to sites of binding for RBMX.

The 5' untranslated region (UTR) creates a Y-like shape and likely has 9 sites of binding for RNA Binding Motif Protein, X-chromosome (RBMX).[8] This gene is implicated in regulating tissue-specific gene expression.

Protein

BTBD16 protein isoform A contains 507 amino acids and has a molecular weight of approximately 58.5 kDa.[9] There is a marginally higher composition of phenylalanine (F) within this protein than the average human protein.[10] Otherwise, there are no notable charged domains or transmembrane segments. It has an isoelectric point of 9.3, meaning it will be positively charged in the general cell environment.[11]

Localization

BTBD16 protein isoform A has a nuclear localization sequence (NLS) of PKKTKEK, meaning it can localize within the nucleus of the cell.[12] It is also predicted to localize within the cytosol and/or the mitochondria, all of which are consistent with predicted protein interactions.

Structure

There are 20 alpha helices and 15 beta strands within the structure of this protein.[13] Most models for BTBD16 are based on Kelch-like proteins and BTB domain-containing regions and Kelch domains within proteins that are more studied than this one.[14] This further confirms the presences of the BTB and BACK domains within the BTBD16 gene and protein.

Motifs and modification sites

There are few high scoring post-translational modification sites within the main isoform of BTBD16:[15]

  • LIG_FAT_LD1: part of the paxillin leucine-rich repeat motif family; recognized by focal adhesion proteins involved in regulation of the cytoskeleton.
  • LIG_PAM2_1: peptide ligand binding motif; binds to domain found in polyA-binding proteins and E3 ubiquitin ligases.
  • DOC_MAPK_FxFP_2 : helps regulate the mitogen-activated protein kinase pathway (MAPK), transferring cell signals from external stimuli to internal responses.

There are 22 high scoring protein kinase C (PKC) sites within BTBD16 as well.[16]

Structural Model of Homo sapiens BTBD16 from I-TASSER.[13] Colored N-terminus in darkest blue to C-terminus in darkest red.

Protein interactions

BTBD16 may interact with multiple different proteins. It is co-expressed with both pleckstrin homology domain-containing family A member 1 (PLEKHA1) and transforming acidic coiled-coil-containing protein 16 (TACC2).[17] These two genes are directly down and upstream of BTBD16, respectively.[2]

Proteins found to interact with BTBD16 through two-hybrid experiments are PAX-interacting protein 1 (PAXIP1) and rhophilin associated tail protein 1 (ROPN1).[18]

Other proteins mentioned in papers alongside BTBD16 are coiled-coil domain containing 191 (CCDC191), DPY19L3, age-related maculopathy susceptibility 2 (ARMS2), and NADH dehydrogenase complex I assembly factor 6 (NDUFAF6).[17]

Evolution

BTBD16 has been found in species as far back as cartilaginous fishes, but not jawless fish, invertebrates, or bacteria.[19]

Select Orthologs of Homo sapiens BTBD16
Organism Common Name Taxonomic Group Date of Divergence (MYA) Accession Number Sequence Length (aa) Sequence Identity (%) Sequence Similarity (%)
Homo sapiens Human Primates 0 NP_001305118.1 507 100 100
Pongo abelii Sumatran Orangutan Primates 15 XP_024109654.3 507 97 98
Macaca fascicularis Crab-eating macaque Primates 29 XP_065377624.1 505 91 94
Mus musculus Mouse Rodentia 87 XP_036009074.1 522 70 83
Monodelphis domestica Gray Short-tailed Opossum Didelphimorphia 160 XP_016288166.1 517 56 68
Tachyglossus aculeatus Short-beaked Echidna Monotremata 180 XP_038614241.1 561 47 62
Aquila chrysaetos chrysaetos Golden Eagle Accipitridae 319 XP_029886573.1 210 55 68
Athene cunicularia Burrowing Owl Stringformes 319 XP_026707353.1 140 52 61
Mauremys mutica Yellow Pond Turtle Testudines 319 XP_044880231.1 506 51 69
Podarcis muralis Common Wall Lizard Squamata 319 XP_028584296.1 617 46 62
Varanus komodoensis Komodo Dragon Squamata 319 XP_044306495.1 615 45 61
Candoia aspera Papuan Ground Boa Squamata 319 XP_063163358.1 615 43 60
Ambystoma mexicanum Axolotl Urodela 352 XP_069468080.1 625 41 57
Geotrypetes seraphini Gabon Caecilian Gymnophiona 352 XP_033798618.1 582 38 53
Erpetoichthys calabaricus Reedfish Polypteriformes 429 XP_028648400.2 333 42 68
Polyodon spathula American Sawfish Acipenseriformes 429 XP_041123341.1 598 38 55
Hypanus sabinus Atlantic Stingray Myliobatiformes 462 XP_059803758.1 509 37 58
Callorhinchus milli Elephant Shark Chimaeriformes 462 XP_042192794.1 624 36 53
Amblyraja radiata Thorny Skate Rajiformes 462 XP_032890644.1 543 34 54

Clinical significance

Various studies, mainly Genome Wide Association Studies (GWAS), note variants in the BTBD16 in association with type 2 diabetes,[20][21] bipolar disorder,[22][23] Alzheimer's disease,[20][24] and multiple cancers like bladder[25] and breast.[26]

There are no known malignant variations within the BTBD16 gene specifically that are of clinical significance. One single nucleotide polymorphism (SNP) has been labeled as a variant of unknown significance (VUS) in correlation with malignant prostate tumor.[27] This is a missense mutation in proline 29 that becomes a serine.

Conceptual translation

First half of Homo sapiens BTBD16 conceptual translation. Includes 5'UTR and amino acids 1–273.
Second half of Homo sapiens conceptual translation. Contains amino acids 274-507 and the 3' UTR.
Key for Homo sapiens BTBD16 Conceptual Translation.

References

  1. ↑ "UCSB Genome Brower GRCh38/hg38 Assembly of BTBD16 BLAT". https://genome.ucsc.edu/cgi-bin/hgBlat. 
  2. ↑ 2.0 2.1 "NCBI Gene: BTBD16". https://www.ncbi.nlm.nih.gov/gene/118663. 
  3. ↑ "NCBI GEO Profiles: BTBD16- Normal human tissue expression profiling (HG-U958B)". https://www.ncbi.nlm.nih.gov/geoprofiles/2894839. 
  4. ↑ "Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics *" (in English). Molecular & Cellular Proteomics 13 (2): 397–406. 2014-02-01. doi:10.1074/mcp.M113.035600. PMID 33498127. 
  5. ↑ "NCBI Nucleotide: BTBD16 isoform a". 30 April 2025. https://www.ncbi.nlm.nih.gov/nuccore/NM_001318189.3. 
  6. ↑ "Homo sapiens BTB domain containing 16 (BTBD16), transcript variant 1, mRNA" (in en-US). NCBI. 2025-04-30. http://www.ncbi.nlm.nih.gov/nuccore/NM_001318189.3. 
  7. ↑ "RNA Folding Form". https://www.unafold.org/mfold/applications/rna-folding-form.php. 
  8. ↑ "RBPDB: The database of RNA-binding specificities". http://rbpdb.ccbr.utoronto.ca/. 
  9. ↑ "Gene Cards BTBD16 Gene". https://www.genecards.org/cgi-bin/carddisp.pl?gene=BTBD16. 
  10. ↑ "SAPS Sequence Statistics". https://www.ebi.ac.uk/jdispatcher/seqstats/saps?species=HUMAN. 
  11. ↑ "Expasy: Compute pI/MW". https://web.expasy.org/cgi-bin/compute_pi/pi_tool.cgi. 
  12. ↑ "PSORT II: NUCDISC of BTBD16". https://psort.hgc.jp/cgi-bin/runpsort.pl. 
  13. ↑ 13.0 13.1 "COFACTOR: improved protein function prediction by combining structure, sequence and protein-protein interaction information". Nucleic Acids Research 45 (W1): W291–W299. July 2017. doi:10.1093/nar/gkx366. PMID 28472402. 
  14. ↑ "Phyre2.2: A Community Resource for Template-based Protein Structure Prediction". Journal of Molecular Biology 437 (15). August 2025. doi:10.1016/j.jmb.2025.168960. PMID 40133783. 
  15. ↑ "ELM-the Eukaryotic Linear Motif resource-2024 update". Nucleic Acids Research 52 (D1): D442–D455. January 2024. doi:10.1093/nar/gkad1058. PMID 37962385. 
  16. ↑ "NetPhos 3.1 - DTU Health Tech - Bioinformatic Services". https://services.healthtech.dtu.dk/services/NetPhos-3.1/. 
  17. ↑ 17.0 17.1 "STRINGdb 12.0". https://string-db.org/cgi/network?taskId=bnZr8vHo0EYp&sessionId=bES8eT5mSpfd. 
  18. ↑ "BioGRID 5.0- BTBD16 (C10orf87)". https://thebiogrid.org/125616/summary/homo-sapiens/btbd16.html. 
  19. ↑ "NCBI BLAST: protein to protein". https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastp&PAGE_TYPE=BlastSearch&LINK_LOC=blasthome. 
  20. ↑ 20.0 20.1 "Shared (epi)genomic background connecting neurodegenerative diseases and type 2 diabetes". World Journal of Diabetes 11 (5): 155–164. May 2020. doi:10.4239/wjd.v11.i5.155. PMID 32477452. 
  21. ↑ "Author Correction: Exploring the shared genetic architecture of type 2 diabetes mellitus and bone mineral density". Archives of Osteoporosis 20 (1): 94. July 2025. doi:10.1007/s11657-025-01581-w. PMID 40663165. 
  22. ↑ "Genome-wide association study of bipolar disorder in European American and African American individuals". Molecular Psychiatry 14 (8): 755–763. August 2009. doi:10.1038/mp.2009.43. PMID 19488044. 
  23. ↑ "Shared genetics and causal relationships between migraine and thyroid function traits". Cephalalgia 43 (2). February 2023. doi:10.1177/03331024221139253. PMID 36739509. 
  24. ↑ "Brain-wide genome-wide colocalization study for integrating genetics, transcriptomics and brain morphometry in Alzheimer's disease". NeuroImage 280. October 2023. doi:10.1016/j.neuroimage.2023.120346. PMID 37634885. 
  25. ↑ "Identification of Prognosis-Related Genes in Bladder Cancer Microenvironment across TCGA Database". BioMed Research International 2020 (1). 2020-11-04. doi:10.1155/2020/9143695. PMID 33204728. 
  26. ↑ "Profiling Receptor Tyrosine Kinase Fusions in Chinese Breast Cancers". Frontiers in Oncology 11. 2021-09-28. doi:10.3389/fonc.2021.741142. PMID 34650924. 
  27. ↑ ClinVar. "NM_144587.5(BTBD16):c.82C>T (p.Pro28Ser) AND Prostate cancer - ClinVar - NCBI" (in en). https://www.ncbi.nlm.nih.gov/clinvar/RCV000149342.3/. 



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