{{Short description|Gene on human chromosome 10}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox gene}} '''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.<ref>{{Cite web | title = UCSB Genome Brower GRCh38/hg38 Assembly of BTBD16 BLAT | url = https://genome.ucsc.edu/cgi-bin/hgBlat | website = UCSB Genome Browser }}</ref> The sequence spans 66,682 base pairs and contains 16 exons.<ref name="citee7f202ae">{{Cite web | title = NCBI Gene: BTBD16 | url = https://www.ncbi.nlm.nih.gov/gene/118663 }}</ref> 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.<ref>{{Cite web | title = NCBI GEO Profiles: BTBD16- Normal human tissue expression profiling (HG-U958B) | url = https://www.ncbi.nlm.nih.gov/geoprofiles/2894839 }}</ref> 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.<ref>{{cite journal | title = Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics * | journal = Molecular & Cellular Proteomics | volume = 13 | issue = 2 | pages = 397–406 | date = 2014-02-01 | pmid = 33498127 | doi = 10.1074/mcp.M113.035600 | language = English | doi-access = free | vauthors = Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A, Edlund K, Asplund A, Sjöstedt E, Lundberg E, Szigyarto CA, Skogs M, Takanen JO, Berling H, Tegel H, Mulder J, Nilsson P, Schwenk JM, Lindskog C, Danielsson F, Mardinoglu A, Sivertsson Å, von Feilitzen K, Forsberg M, Zwahlen M, Olsson I, Navani S }}</ref>
== 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.<ref>{{Cite web | title = NCBI Nucleotide: BTBD16 isoform a | date = 30 April 2025 | url = https://www.ncbi.nlm.nih.gov/nuccore/NM_001318189.3 }}</ref> {| class="wikitable" |+ ''Homo sapiens'' BTBD16 Transcript Variants and Protein Isoforms ! Transcript Variant ! Accession # ! Nucleotide Length ! Protein Isoform ! Accession # ! Amino Acid Length |- | 1 | [https://www.ncbi.nlm.nih.gov/nuccore/NM_001318189.3 NM_001318189.3] | 1859 | a | [https://www.ncbi.nlm.nih.gov/protein/NP_001305118.1 NP_001305118.1] | 507 |- | 2 | [https://www.ncbi.nlm.nih.gov/nuccore/NM_144587.5 NM_144587.5] | 1856 | b | [https://www.ncbi.nlm.nih.gov/protein/NP_653188.2 NP_653188.2] | 506 |- | X1 | [https://www.ncbi.nlm.nih.gov/nuccore/XM_011539239.3 XM_011539239.3] | 1739 | X1 | [https://www.ncbi.nlm.nih.gov/protein/XP_011537541.1 XP_011537541.1] | 467 |- | X2 | [https://www.ncbi.nlm.nih.gov/nuccore/XM_011539240.3 XM_011539240.3] | 1715 | X2 | [https://www.ncbi.nlm.nih.gov/protein/XP_011537542.1 XP_011537542.1] | 459 |- | X3 | [https://www.ncbi.nlm.nih.gov/nuccore/XM_011539241.3 XM_011539241.3] | 1658 | X3 | [https://www.ncbi.nlm.nih.gov/protein/XP_011537543.1 XP_011537543.1] | 440 |- | X4 | [https://www.ncbi.nlm.nih.gov/nuccore/XM_011539242.3 XM_011539242.3] | 1538 | X4 | [https://www.ncbi.nlm.nih.gov/protein/XP_011537544.1 XP_011537544.1] | 400 |- | X5 | [https://www.ncbi.nlm.nih.gov/nuccore/XM_017015637.2 XM_017015637.2] | 2563 | X5 | [https://www.ncbi.nlm.nih.gov/protein/XP_016871126.1 XP_016871126.1] | 338 |}
=== Regulation === There are few noted regulation sites within transcript variant 1:<ref>{{Cite journal | title = Homo sapiens BTB domain containing 16 (BTBD16), transcript variant 1, mRNA | journal = NCBI | date = 2025-04-30 | url = http://www.ncbi.nlm.nih.gov/nuccore/NM_001318189.3 | language = en-US }}</ref>
* 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) thumb|''Homo sapiens'' BTBD16 5' UTR Predicted Structure.<ref>{{Cite web | title = RNA Folding Form | url = https://www.unafold.org/mfold/applications/rna-folding-form.php | access-date = 2025-12-12 | website = www.unafold.org }}</ref> 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).<ref>{{Cite web | title = RBPDB: The database of RNA-binding specificities | url = http://rbpdb.ccbr.utoronto.ca/ | access-date = 2025-12-12 | website = rbpdb.ccbr.utoronto.ca }}</ref> 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.<ref>{{Cite web | title = Gene Cards BTBD16 Gene | url = https://www.genecards.org/cgi-bin/carddisp.pl?gene=BTBD16 }}</ref> There is a marginally higher composition of phenylalanine (F) within this protein than the average human protein.<ref>{{Cite web | title = SAPS Sequence Statistics | url = https://www.ebi.ac.uk/jdispatcher/seqstats/saps?species=HUMAN }}</ref> 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.<ref>{{Cite web | title = Expasy: Compute pI/MW | url = https://web.expasy.org/cgi-bin/compute_pi/pi_tool.cgi }}</ref>
=== Localization === BTBD16 protein isoform A has a nuclear localization sequence (NLS) of PKKTKEK, meaning it can localize within the nucleus of the cell.<ref>{{Cite web | title = PSORT II: NUCDISC of BTBD16 | url = https://psort.hgc.jp/cgi-bin/runpsort.pl }}</ref> 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.<ref name="Zhang_2017" /> 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.<ref>{{cite journal | vauthors = Powell HR, Islam SA, David A, Sternberg MJ | title = Phyre2.2: A Community Resource for Template-based Protein Structure Prediction | journal = Journal of Molecular Biology | volume = 437 | issue = 15 | date = August 2025 | pmid = 40133783 | pmc = 7617537 | doi = 10.1016/j.jmb.2025.168960 | article-number = 168960 }}</ref> 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:<ref>{{cite journal | vauthors = Kumar M, Michael S, Alvarado-Valverde J, Zeke A, Lazar T, Glavina J, Nagy-Kanta E, Donagh JM, Kalman ZE, Pascarelli S, Palopoli N, Dobson L, Suarez CF, Van Roey K, Krystkowiak I, Griffin JE, Nagpal A, Bhardwaj R, Diella F, Mészáros B, Dean K, Davey NE, Pancsa R, Chemes LB, Gibson TJ | title = ELM-the Eukaryotic Linear Motif resource-2024 update | journal = Nucleic Acids Research | volume = 52 | issue = D1 | pages = D442–D455 | date = January 2024 | pmid = 37962385 | pmc = 10767929 | doi = 10.1093/nar/gkad1058 }}</ref>
* 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.<ref>{{Cite web | title = NetPhos 3.1 - DTU Health Tech - Bioinformatic Services | url = https://services.healthtech.dtu.dk/services/NetPhos-3.1/ | access-date = 2025-12-12 | website = services.healthtech.dtu.dk }}</ref>thumb|Structural Model of ''Homo sapiens'' BTBD16 from I-TASSER.<ref name="Zhang_2017">{{cite journal | vauthors = Zhang C, Freddolino L, Zhang Y | title = COFACTOR: improved protein function prediction by combining structure, sequence and protein-protein interaction information | journal = Nucleic Acids Research | volume = 45 | issue = W1 | pages = W291–W299 | date = July 2017 | pmid = 28472402 | pmc = 5793808 | doi = 10.1093/nar/gkx366 }}</ref> 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).<ref name="citea88fbf4c">{{Cite web | title = STRINGdb 12.0 | url = https://string-db.org/cgi/network?taskId=bnZr8vHo0EYp&sessionId=bES8eT5mSpfd }}</ref> These two genes are directly down and upstream of BTBD16, respectively.<ref name="citee7f202ae" />
Proteins found to interact with BTBD16 through two-hybrid experiments are PAX-interacting protein 1 (PAXIP1) and rhophilin associated tail protein 1 (ROPN1).<ref>{{Cite web | title = BioGRID 5.0- BTBD16 (C10orf87) | url = https://thebiogrid.org/125616/summary/homo-sapiens/btbd16.html }}</ref>
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).<ref name="citea88fbf4c" />
=== Evolution === BTBD16 has been found in species as far back as cartilaginous fishes, but not jawless fish, invertebrates, or bacteria.<ref>{{Cite web | title = NCBI BLAST: protein to protein | url = https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastp&PAGE_TYPE=BlastSearch&LINK_LOC=blasthome }}</ref> {| class="wikitable" |+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,<ref name="Caputo_2020">{{cite journal | vauthors = Caputo V, Termine A, Strafella C, Giardina E, Cascella R | title = Shared (epi)genomic background connecting neurodegenerative diseases and type 2 diabetes | journal = World Journal of Diabetes | volume = 11 | issue = 5 | pages = 155–164 | date = May 2020 | pmid = 32477452 | pmc = 7243483 | doi = 10.4239/wjd.v11.i5.155 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Feng X, Xu H, Guo Q, Wang Z, Ba R, Xuan K, Ban J | title = Author Correction: Exploring the shared genetic architecture of type 2 diabetes mellitus and bone mineral density | journal = Archives of Osteoporosis | volume = 20 | issue = 1 | pages = 94 | date = July 2025 | pmid = 40663165 | doi = 10.1007/s11657-025-01581-w | article-number = 94 }}</ref> bipolar disorder,<ref>{{cite journal | vauthors = Smith EN, Bloss CS, Badner JA, Barrett T, Belmonte PL, Berrettini W, Byerley W, Coryell W, Craig D, Edenberg HJ, Eskin E, Foroud T, Gershon E, Greenwood TA, Hipolito M, Koller DL, Lawson WB, Liu C, Lohoff F, McInnis MG, McMahon FJ, Mirel DB, Murray SS, Nievergelt C, Nurnberger J, Nwulia EA, Paschall J, Potash JB, Rice J, Schulze TG, Scheftner W, Panganiban C, Zaitlen N, Zandi PP, Zöllner S, Schork NJ, Kelsoe JR | title = Genome-wide association study of bipolar disorder in European American and African American individuals | journal = Molecular Psychiatry | volume = 14 | issue = 8 | pages = 755–763 | date = August 2009 | pmid = 19488044 | pmc = 3035981 | doi = 10.1038/mp.2009.43 }}</ref><ref>{{cite journal | vauthors = Tasnim S, Wilson SG, Walsh JP, Nyholt DR | title = Shared genetics and causal relationships between migraine and thyroid function traits | journal = Cephalalgia | volume = 43 | issue = 2 | date = February 2023 | pmid = 36739509 | doi = 10.1177/03331024221139253 | article-number = 03331024221139253 }}</ref> Alzheimer's disease,<ref name="Caputo_2020" /><ref>{{cite journal | vauthors = Bao J, Wen J, Wen Z, Yang S, Cui Y, Yang Z, Erus G, Saykin AJ, Long Q, Davatzikos C, Shen L | title = Brain-wide genome-wide colocalization study for integrating genetics, transcriptomics and brain morphometry in Alzheimer's disease | journal = NeuroImage | volume = 280 | article-number = 120346 | date = October 2023 | pmid = 37634885 | pmc = 10552907 | doi = 10.1016/j.neuroimage.2023.120346 }}</ref> and multiple cancers like bladder<ref>{{cite journal | vauthors = Zhao X, Tang Y, Ren H, Lei Y | title = Identification of Prognosis-Related Genes in Bladder Cancer Microenvironment across TCGA Database | journal = BioMed Research International | volume = 2020 | issue = 1 | date = 2020-11-04 | pmid = 33204728 | pmc = 7658688 | doi = 10.1155/2020/9143695 | doi-access = free | article-number = 9143695 }}</ref> and breast.<ref>{{cite journal | vauthors = Tao Z, Liu J, Li T, Xu H, Chen K, Zhang J, Zhou H, Sun J, Han J, Guo Z, Yang H, Cao WM, Hu X | title = Profiling Receptor Tyrosine Kinase Fusions in Chinese Breast Cancers | journal = Frontiers in Oncology | volume = 11 | date = 2021-09-28 | pmid = 34650924 | pmc = 8506003 | doi = 10.3389/fonc.2021.741142 | doi-access = free | article-number = 741142 }}</ref>
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.<ref>{{Cite web | title = NM_144587.5(BTBD16):c.82C>T (p.Pro28Ser) AND Prostate cancer - ClinVar - NCBI | last = ClinVar | url = https://www.ncbi.nlm.nih.gov/clinvar/RCV000149342.3/ | access-date = 2025-12-04 | website = www.ncbi.nlm.nih.gov | language = en }}</ref> This is a missense mutation in proline 29 that becomes a serine.
== Conceptual translation == thumb|First half of ''Homo sapiens'' BTBD16 conceptual translation. Includes 5'UTR and amino acids 1–273.thumb|Second half of ''Homo sapiens'' conceptual translation. Contains amino acids 274-507 and the 3' UTR. thumb|Key for ''Homo sapiens'' BTBD16 Conceptual Translation.
== References == {{reflist}}
Category:Proteins