{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T01:46:45Z","timestamp":1782438405920,"version":"3.54.5"},"reference-count":95,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>KCTD proteins exhibit significant structural complexity, arising from their modular organization, oligomerization, and intricate biological partnerships. Although their biological importance has been assessed for two decades, the biochemical basis of their activities is only partially understood. This is certainly due to the limited structural information that was available until a few years ago. Fortunately, some recent insightful structural studies and the advent of machine-learning-based approaches are rapidly changing the scenario. By surveying the literature and structural databases and integrating this information with ad hoc 3D-structure predictions, we provide a detailed view of the structural biology of these proteins at different levels: individual domains, full-length oligomers, functional hetero-oligomers formed by different family members, and complexes with functional partners. Collectively, these surveys and analyses provide insights into the family\u2019s evolutionary history and its structure\u2013function relationships. The family-wide coverage of structural information also indicates the extent to which structural similarities are reflected in functional analogies. Finally, the potential functional implications of the intricate architecture of these multimeric proteins and the tendency of their members to hetero-oligomerize are discussed from a functional perspective.<\/jats:p>","DOI":"10.3390\/ijms27135745","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:49:23Z","timestamp":1782434963000},"page":"5745","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Global Analysis of the Complex Structural Organization of KCTD Proteins and Their Functional Implications"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7862-9448","authenticated-orcid":false,"given":"Nicole","family":"Balasco","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology and Pathology (IBPM), CNR c\/o Department of Chemistry, Sapienza University of Rome, Piazzale A. Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6431-2677","authenticated-orcid":false,"given":"Luciana","family":"Esposito","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging (IBB), CNR, Via P. Castellino 111, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4688-1080","authenticated-orcid":false,"given":"Simone","family":"Di Micco","sequence":"additional","affiliation":[{"name":"European Biomedical Research Institute of Salerno (EBRIS), Via S. De Renzi 50, 84125 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3032-3375","authenticated-orcid":false,"given":"Luigi","family":"Vitagliano","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging (IBB), CNR, Via P. Castellino 111, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12964-021-00737-8","article-title":"The Emerging Role of the KCTD Proteins in Cancer","volume":"19","author":"Angrisani","year":"2021","journal-title":"Cell Commun. Signal."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1111\/cns.13156","article-title":"KCTD: A New Gene Family Involved in Neurodevelopmental and Neuropsychiatric Disorders","volume":"25","author":"Teng","year":"2019","journal-title":"CNS Neurosci. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.bbrc.2023.02.068","article-title":"Kctd17-Mediated Chop Degradation Promotes Adipogenic Differentiation","volume":"653","author":"Shin","year":"2023","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_4","first-page":"158514","article-title":"KCTD1: A Novel Modulator of Adipogenesis through the Interaction with the Transcription Factor AP2\u03b1","volume":"1864","author":"Pirone","year":"2019","journal-title":"Biochim. Biophys. Acta BBA-Mol. Cell Biol. Lipids"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.ijbiomac.2018.04.078","article-title":"The Essential Player in Adipogenesis GRP78 Is a Novel KCTD15 Interactor","volume":"115","author":"Smaldone","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.seizure.2026.01.005","article-title":"KCTD7-Related Progressive Myoclonic Epilepsy: Clinical and Genetic Characterization of Six Indian Patients and Review of Literature","volume":"135","author":"Sangeeth","year":"2026","journal-title":"Seizure Eur. J. Epilepsy"},{"key":"ref_7","first-page":"115","article-title":"KCTD7-related Progressive Myoclonus Epilepsy","volume":"18","year":"2016","journal-title":"Epileptic Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/jid.2014.413","article-title":"Genetics of Aplasia Cutis Reveal Novel Regulators of Skin Morphogenesis","volume":"135","author":"Marneros","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.ajhg.2013.03.002","article-title":"Mutations in KCTD1 Cause Scalp-Ear-Nipple Syndrome","volume":"92","author":"Marneros","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e174138","DOI":"10.1172\/JCI174138","article-title":"KCTD1\/KCTD15 Complexes Control Ectodermal and Neural Crest Cell Functions, and Their Impairment Causes Aplasia Cutis","volume":"134","author":"Raymundo","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1136\/jmg-2023-109531","article-title":"BTB Domain Mutations Perturbing KCTD15 Oligomerisation Cause a Distinctive Frontonasal Dysplasia Syndrome","volume":"61","author":"Miller","year":"2024","journal-title":"J. Med. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41586-025-09585-9","article-title":"KCTD10 Is a Sensor for Co-Directional Transcription\u2013Replication Conflicts","volume":"648","author":"Kloeber","year":"2025","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chen, B., Kloeber, J.A., Huang, J., and Lou, Z. (2026). KCTD10 Resolves Co-Directional Transcription\u2013Replication Conflicts. Trends Cell Biol.","DOI":"10.1016\/j.tcb.2026.04.010"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e2400464121","DOI":"10.1073\/pnas.2400464121","article-title":"KCTD10 p.C124W Variant Contributes to Schizophrenia by Attenuating LLPS-Mediated Synapse Formation","volume":"121","author":"Mu","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41418-023-01246-6","article-title":"SALL4 Is a CRL3REN\/KCTD11 Substrate That Drives Sonic Hedgehog-Dependent Medulloblastoma","volume":"31","author":"Loricchio","year":"2024","journal-title":"Cell Death Differ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e2320655121","DOI":"10.1073\/pnas.2320655121","article-title":"The CRL3KCTD10 Ubiquitin Ligase\u2013USP18 Axis Coordinately Regulates Cystine Uptake and Ferroptosis by Modulating SLC7A11","volume":"121","author":"Zhou","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e2315707121","DOI":"10.1073\/pnas.2315707121","article-title":"KCTD10 Regulates Brain Development by Destabilizing Brain Disorder\u2013Associated Protein KCTD13","volume":"121","author":"Cheng","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1038\/s41418-023-01174-5","article-title":"KCTD13-Mediated Ubiquitination and Degradation of GluN1 Regulates Excitatory Synaptic Transmission and Seizure Susceptibility","volume":"30","author":"Gu","year":"2023","journal-title":"Cell Death Differ."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/7854_2020_147","article-title":"Structural Basis of GABAB Receptor Regulation and Signaling","volume":"Volume 52","author":"Vlachou","year":"2020","journal-title":"Behavioral Neurobiology of GABAB Receptor Function"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nature24470","article-title":"Kctd13 Deletion Reduces Synaptic Transmission via Increased RhoA","volume":"551","author":"Escamilla","year":"2017","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nature22376","article-title":"Genetic Wiring Maps of Single-Cell Protein States Reveal an off-Switch for GPCR Signalling","volume":"546","author":"Brockmann","year":"2017","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nature11091","article-title":"KCTD13 Is a Major Driver of Mirrored Neuroanatomical Phenotypes of the 16p11.2 Copy Number Variant","volume":"485","author":"Golzio","year":"2012","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature08964","article-title":"Native GABAB Receptors Are Heteromultimers with a Family of Auxiliary Subunits","volume":"465","author":"Schwenk","year":"2010","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2013","article-title":"Histone Deacetylase and Cullin3\u2013RENKCTD11 Ubiquitin Ligase Interplay Regulates Hedgehog Signalling through Gli Acetylation","volume":"12","author":"Canettieri","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.molmed.2005.10.005","article-title":"Hedgehog Checkpoints in Medulloblastoma: The Chromosome 17p Deletion Paradigm","volume":"11","author":"Ferretti","year":"2005","journal-title":"Trends Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"18237","DOI":"10.1038\/s41598-021-97775-6","article-title":"KCTD15 Deregulation Is Associated with Alterations of the NF-\u03baB Signaling in Both Pathological and Physiological Model Systems","volume":"11","author":"Smaldone","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/s13402-025-01044-x","article-title":"Exosomes Delivering miR-129-5p Combined with Sorafenib Ameliorate Hepatocellular Carcinoma Progression via the KCTD1\/HIF-1\u03b1\/VEGF Pathway","volume":"48","author":"Zhu","year":"2025","journal-title":"Cell Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"218301","DOI":"10.1016\/j.canlet.2026.218301","article-title":"ZBTB20 Promotes Malignancy and Stemness in Lung Squamous Cell Carcinoma through the Transcriptional Repression of KCTD1 and Activation of Hedgehog Signaling","volume":"643","author":"Wang","year":"2026","journal-title":"Cancer Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41420-026-02975-6","article-title":"KCTD1 Stabilizes C-Myc to Upregulate PD-L1 and Suppress Anti-Tumor Immunity in Hepatocellular Carcinoma","volume":"12","author":"Zhong","year":"2026","journal-title":"Cell Death Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e71563","DOI":"10.1096\/fj.202503381R","article-title":"KCTD15 Enhances Stem Cell-Like Properties and Promotes Triple-Negative Breast Cancer Progression Through KLF4\/\u03b2-Catenin Signaling","volume":"40","author":"Yao","year":"2026","journal-title":"FASEB J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/jcb.22002","article-title":"The Interaction of KCTD1 with Transcription Factor AP-2\u03b1 Inhibits Its Transactivation","volume":"106","author":"Ding","year":"2009","journal-title":"J. Cell. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2870","DOI":"10.1073\/pnas.1300203110","article-title":"Inhibition of Neural Crest Formation by Kctd15 Involves Regulation of Transcription Factor AP-2","volume":"110","author":"Zarelli","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00784","DOI":"10.1002\/brb3.784","article-title":"Influence of TFAP 2B and KCTD 15 Genetic Variability on Personality Dimensions in Anorexia and Bulimia Nervosa","volume":"7","author":"Albuquerque","year":"2017","journal-title":"Brain Behav."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e2406686121","DOI":"10.1073\/pnas.2406686121","article-title":"KCTD1 Regulation of Adenylyl Cyclase Type 5 Adjusts Striatal cAMP Signaling","volume":"121","author":"Liao","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"110813","DOI":"10.1016\/j.jbc.2025.110813","article-title":"Pathogenic Variants in KCTD1 Disrupt cAMP Signaling and Cellular Communication Associated with Developmental Pathways","volume":"301","author":"Liao","year":"2025","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Smaldone, G., Pecoraro, G., Pane, K., Franzese, M., Ruggiero, A., Vitagliano, L., and Salvatore, M. (2023). The Oncosuppressive Properties of KCTD1: Its Role in Cell Growth and Mobility. Biology, 12.","DOI":"10.3390\/biology12030481"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Buono, L., Iside, C., Pecoraro, G., De Matteo, A., Beneduce, G., Penta De Vera d\u2019Aragona, R., Parasole, R., Mirabelli, P., Vitagliano, L., and Salvatore, M. (2023). A Comprehensive Analysis of the Expression Profiles of KCTD Proteins in Acute Lymphoblastic Leukemia: Evidence of Selective Expression of KCTD1 in T-ALL. J. Clin. Med., 12.","DOI":"10.3390\/jcm12113669"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100926","DOI":"10.1016\/j.neo.2023.100926","article-title":"KCTD1 Is a New Modulator of the KCASH Family of Hedgehog Suppressors","volume":"43","author":"Bellardinelli","year":"2023","journal-title":"Neoplasia"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Coppola, L., Baselice, S., Messina, F., Giannatiempo, R., Farina, A., Vitagliano, L., Smaldone, G., and Salvatore, M. (2022). KCTD15 Is Overexpressed in Her2+ Positive Breast Cancer Patients and Its Silencing Attenuates Proliferation in SKBR3 CELL LINE. Diagnostics, 12.","DOI":"10.3390\/diagnostics12030591"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"20108","DOI":"10.1038\/s41598-019-56701-7","article-title":"KCTD15 Is Overexpressed in Human Childhood B-Cell Acute Lymphoid Leukemia","volume":"9","author":"Smaldone","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41389-019-0175-6","article-title":"KCTD15 Inhibits the Hedgehog Pathway in Medulloblastoma Cells by Increasing Protein Levels of the Oncosuppressor KCASH2","volume":"8","author":"Spiombi","year":"2019","journal-title":"Oncogenesis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/s42003-024-05880-9","article-title":"KCTD15 Acts as an Anti-Tumor Factor in Colorectal Cancer Cells Downstream of the Demethylase FTO and the m6A Reader YTHDF2","volume":"7","author":"Zhang","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1016\/j.jid.2024.05.014","article-title":"Aplasia Cutis Congenita Pathomechanisms Reveal Key Regulators of Skin and Skin Appendage Morphogenesis","volume":"144","author":"Marneros","year":"2024","journal-title":"J. Investig. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10519","DOI":"10.1038\/s41598-019-46911-4","article-title":"Molecular Basis of the Scalp-Ear-Nipple Syndrome Unraveled by the Characterization of Disease-Causing KCTD1 Mutants","volume":"9","author":"Smaldone","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_45","first-page":"3895","article-title":"KCTD1 Mutants in Scalp-ear-nipple Syndrome and AP-2\u03b1 P59A in Char Syndrome Reciprocally Abrogate Their Interactions, but Can Regulate Wnt\/\u0392-catenin Signaling","volume":"22","author":"Hu","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.jid.2025.09.371","article-title":"KCTD1\/KCTD15-Mediated Repression of AP-2\u03b1\/AP-2\u03b2 Is Required for Proper Skin Appendage Development and Epidermal Homeostasis","volume":"146","author":"Senapati","year":"2026","journal-title":"J. Investig. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"dev191973","DOI":"10.1242\/dev.191973","article-title":"Kctd15 Regulates Nephron Segment Development by Repressing Tfap2a Activity","volume":"147","author":"Chambers","year":"2020","journal-title":"Development"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1093\/brain\/aww244","article-title":"Pathogenic Variants in KCTD7 Perturb Neuronal K+ Fluxes and Glutamine Transport","volume":"139","author":"Moen","year":"2016","journal-title":"Brain"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Smaldone, G., Pirone, L., Balasco, N., Di Gaetano, S., Pedone, E.M., and Vitagliano, L. (2015). Cullin 3 Recognition Is Not a Universal Property among KCTD Proteins. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126808"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41586-019-0990-0","article-title":"Structural Basis for KCTD-Mediated Rapid Desensitization of GABAB Signalling","volume":"567","author":"Zheng","year":"2019","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1042\/BCJ20170527","article-title":"Structural Complexity in the KCTD Family of Cullin3-Dependent E3 Ubiquitin Ligases","volume":"474","author":"Pinkas","year":"2017","journal-title":"Biochem. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8819","DOI":"10.1021\/acs.jmedchem.9b01087","article-title":"Targeting the \u03b3-Aminobutyric Acid Type B (GABAB) Receptor Complex: Development of Inhibitors Targeting the K+ Channel Tetramerization Domain (KCTD) Containing Proteins\/GABAB Receptor Protein\u2013Protein Interaction","volume":"62","author":"Sereikaite","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8370","DOI":"10.1073\/pnas.1903024116","article-title":"Structural Basis for Auxiliary Subunit KCTD16 Regulation of the GABAB Receptor","volume":"116","author":"Zuo","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jmb.2015.08.019","article-title":"Structural Insights into KCTD Protein Assembly and Cullin3 Recognition","volume":"428","author":"Ji","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.str.2024.07.023","article-title":"A BTB Extension and Ion-Binding Domain Contribute to the Pentameric Structure and TFAP2A Binding of KCTD1","volume":"32","author":"Pinkas","year":"2024","journal-title":"Structure"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"134390","DOI":"10.1016\/j.ijbiomac.2024.134390","article-title":"Structural Studies of KCTD1 and Its Disease-Causing Mutant P20S Provide Insights into the Protein Function and Misfunction","volume":"277","author":"Balasco","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jmb.2009.01.030","article-title":"Pentameric Assembly of Potassium Channel Tetramerization Domain-Containing Protein 5","volume":"387","author":"Dementieva","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"eadg8369","DOI":"10.1126\/sciadv.adg8369","article-title":"Structural Basis for the Ubiquitination of G Protein \u0392\u03b3 Subunits by KCTD5\/Cullin3 E3 Ligase","volume":"9","author":"Jiang","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e2315018121","DOI":"10.1073\/pnas.2315018121","article-title":"Structure and Dynamics of a Pentameric KCTD5\/CUL3\/G\u03b2\u03b3 E3 Ubiquitin Ligase Complex","volume":"121","author":"Nguyen","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1093\/genetics\/129.2.385","article-title":"The Drosophila Broad-Complex Encodes a Family of Related Proteins Containing Zinc Fingers","volume":"129","author":"DiBello","year":"1991","journal-title":"Genetics"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"R82","DOI":"10.1186\/gb-2005-6-10-r82","article-title":"Sequence and Structural Analysis of BTB Domain Proteins","volume":"6","author":"Stogios","year":"2005","journal-title":"Genome Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2200179","DOI":"10.1002\/bies.202200179","article-title":"BTB Domains: A Structural View of Evolution, Multimerization, and Protein\u2013Protein Interactions","volume":"45","author":"Bonchuk","year":"2023","journal-title":"BioEssays"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Esposito, L., Balasco, N., Smaldone, G., Berisio, R., Ruggiero, A., and Vitagliano, L. (2021). AlphaFold-Predicted Structures of KCTD Proteins Unravel Previously Undetected Relationships among the Members of the Family. Biomolecules, 11.","DOI":"10.3390\/biom11121862"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Balasco, N., Esposito, L., Smaldone, G., Salvatore, M., and Vitagliano, L. (2024). A Comprehensive Analysis of the Structural Recognition between KCTD Proteins and Cullin 3. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031881"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1002\/bies.201300002","article-title":"Protein Partners of KCTD Proteins Provide Insights about Their Functional Roles in Cell Differentiation and Vertebrate Development","volume":"35","author":"Skoblov","year":"2013","journal-title":"BioEssays"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/2045-3701-3-45","article-title":"The KCTD Family of Proteins: Structure, Function, Disease Relevance","volume":"3","author":"Liu","year":"2013","journal-title":"Cell Biosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/164_2025_766","article-title":"KCTD Family: Emerging Regulators of GPCR Biased Signaling","volume":"Volume 290","author":"Li","year":"2025","journal-title":"Pharmacology of GPCRs Biased Signaling and Agonists"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Balasco, N., and Vitagliano, L. (2025). Structure\u2013Function Correlations in KCTD1\/KCTD15 Proteins. Biol. Life Sci. Forum, 53.","DOI":"10.3390\/blsf2025053002"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1080\/07391102.2015.1090343","article-title":"KCTD5 Is Endowed with Large, Functionally Relevant, Interdomain Motions","volume":"34","author":"Barone","year":"2016","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.biochi.2010.12.014","article-title":"Molecular Organization of the Cullin E3 Ligase Adaptor KCTD11","volume":"93","author":"Correale","year":"2011","journal-title":"Biochimie"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/j.bbapap.2014.04.006","article-title":"Molecular Recognition of Cullin3 by KCTDs: Insights from Experimental and Computational Investigations","volume":"1844","author":"Balasco","year":"2014","journal-title":"Biochim. Biophys. Acta BBA-Proteins Proteom."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/psc.1366","article-title":"Design, Synthesis and Characterization of a Peptide Able to Bind Proteins of the KCTD Family: Implications for KCTD\u2014Cullin 3 Recognition","volume":"17","author":"Pirone","year":"2011","journal-title":"J. Pept. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"De Paola, I., Pirone, L., Palmieri, M., Balasco, N., Esposito, L., Russo, L., Mazz\u00e0, D., Di Marcotullio, L., Di Gaetano, S., and Malgieri, G. (2015). Cullin3-BTB Interface: A Novel Target for Stapled Peptides. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121149"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.biochi.2016.09.013","article-title":"Proteins Involved in Sleep Homeostasis: Biophysical Characterization of INC and Its Partners","volume":"131","author":"Pirone","year":"2016","journal-title":"Biochimie"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1002\/1873-3468.12203","article-title":"The BTB Domains of the Potassium Channel Tetramerization Domain Proteins Prevalently Assume Pentameric States","volume":"590","author":"Smaldone","year":"2016","journal-title":"FEBS Lett."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Balasco, N., Smaldone, G., and Vitagliano, L. (2019). The Structural Versatility of the BTB Domains of KCTD Proteins and Their Recognition of the GABAB Receptor. Biomolecules, 9.","DOI":"10.3390\/biom9080323"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Vitagliano, L., Doti, N., and Balasco, N. (2025). Determinants of Chain Selection and Staggering in Heterotrimeric Collagens: A Comprehensive Review of the Structural Data. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262010134"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Balasco, N., Modjtahedi, N., Monti, A., Ruvo, M., Vitagliano, L., and Doti, N. (2025). CHCHD4 Oxidoreductase Activity: A Comprehensive Analysis of the Molecular, Functional, and Structural Properties of Its Redox-Regulated Substrates. Molecules, 30.","DOI":"10.20944\/preprints202503.2027.v1"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Esposito, L., Balasco, N., and Vitagliano, L. (2022). Alphafold Predictions Provide Insights into the Structural Features of the Functional Oligomers of All Members of the KCTD Family. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113346"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41586-019-1923-7","article-title":"Improved Protein Structure Prediction Using Potentials from Deep Learning","volume":"577","author":"Senior","year":"2020","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly Accurate Protein Structure Prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: Making Protein Folding Accessible to All","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Balasco, N., Esposito, L., and Vitagliano, L. (2025). Structural Biology in the AlphaFold Era: How Far Is Artificial Intelligence from Deciphering the Protein Folding Code?. Biomolecules, 15.","DOI":"10.3390\/biom15050674"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4217","DOI":"10.1016\/j.apsb.2023.07.013","article-title":"KCTD4 Interacts with CLIC1 to Disrupt Calcium Homeostasis and Promote Metastasis in Esophageal Cancer","volume":"13","author":"Zheng","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1523\/JNEUROSCI.2181-16.2016","article-title":"KCTD Hetero-Oligomers Confer Unique Kinetic Properties on Hippocampal GABAB Receptor-Induced K+ Currents","volume":"37","author":"Fritzius","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_86","first-page":"374-IN23","article-title":"Identification and Characterization of KCASH2 and KCASH3, 2 Novel Cullin3 Adaptors Suppressing Histone Deacetylase and Hedgehog Activity in Medulloblastoma","volume":"13","author":"Moretti","year":"2011","journal-title":"Neoplasia"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4318","DOI":"10.1021\/acs.jproteome.1c00292","article-title":"Human Multisubunit E3 Ubiquitin Ligase Required for Heterotrimeric G-Protein \u03b2-Subunit Ubiquitination and Downstream Signaling","volume":"20","author":"Young","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Liao, Y., Sloan, D.C., Widjaja, J.H., and Muntean, B.S. (2023). KCTD5 Forms Hetero-Oligomeric Complexes with Various Members of the KCTD Protein Family. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814317"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Rizk, R., Devost, D., P\u00e9trin, D., and H\u00e9bert, T.E. (2024). KCTD Proteins Have Redundant Functions in Controlling Cellular Growth. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094993"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"9911","DOI":"10.1007\/s11033-012-1858-7","article-title":"TNFAIP1 Interacts with KCTD10 to Promote the Degradation of KCTD10 Proteins and Inhibit the Transcriptional Activities of NF-\u03baB and AP-1","volume":"39","author":"Hu","year":"2012","journal-title":"Mol. Biol. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Li, Q., Kellner, D.A., Hatch, H.A.M., Yumita, T., Sanchez, S., Machold, R.P., Frank, C.A., and Stavropoulos, N. (2017). Conserved Properties of Drosophila Insomniac Link Sleep Regulation and Synaptic Function. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006815"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate Structure Prediction of Biomolecular Interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zarelli, V.E., and Dawid, I.B. (2013). The BTB-Containing Protein Kctd15 Is SUMOylated In Vivo. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075016"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1083\/jcb.201902074","article-title":"Post-Translational Regulation of Ubiquitin Signaling","volume":"218","author":"Song","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Baeza, J., Maureira, D., Gonzalez-Avenda\u00f1o, M., Silva, I., Varela, D., Gonzalez, W., and Cerda, O. (2026). Design of Inhibitory Peptides Based on TRPM4-KCTD5 Interaction. J. Chem. Inf. Model.","DOI":"10.1021\/acs.jcim.6c00534"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5745\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:58:08Z","timestamp":1782435488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":95,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135745"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135745","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]}}}