CYLD (gene)

The CYLD lysine 63 deubiquitinase gene, also termed the CYLD gene, CYLD is an evolutionary ancient gene found to be present as far back on the evolutionary scale as in sponges. In humans, this gene is located in band 12.1 on the long (or "q") arm of chromosome 16 and is known to code (i.e. direct the production of) multiple proteins through the process of alternative splicing.

CYLD
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1IXD, 1WHL, 1WHM, 2VHF
Identifiers
Aliases	CYLD, BRSS, CDMT, CYLD1, CYLDI, EAC, MFT, MFT1, SBS, TEM, USPL2, CYLD lysine 63 deubiquitinase
External IDs	OMIM: 605018; MGI: 1921506; HomoloGene: 9069; GeneCards: CYLD; OMA:CYLD - orthologs
Gene location (Human) Chr. Chromosome 16 (human) Band 16q12.1 Start 50,742,050 bp End 50,801,935 bp
Gene location (Mouse) Chr. Chromosome 8 (mouse) Band 8|8 C3 Start 89,423,656 bp End 89,478,573 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in lateral nuclear group of thalamus Achilles tendon lymph node cartilage tissue external globus pallidus sperm middle temporal gyrus pars reticulata tonsil pars compacta Top expressed in otolith organ utricle olfactory tubercle nucleus accumbens lateral septal nucleus mesenteric lymph nodes ventromedial nucleus anterior amygdaloid area otic vesicle medial geniculate nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function cysteine-type peptidase activity zinc ion binding metal ion binding peptidase activity protein binding thiol-dependent deubiquitinase proline-rich region binding hydrolase activity protein kinase binding Lys63-specific deubiquitinase activity Lys48-specific deubiquitinase activity structural constituent of ribosome Cellular component cytoplasm cytosol centrosome cell projection membrane extrinsic component of cytoplasmic side of plasma membrane plasma membrane spindle microtubule organizing center midbody perinuclear region of cytoplasm cytoplasmic microtubule cytoskeleton microtubule ciliary basal body ciliary tip Biological process regulation of intrinsic apoptotic signaling pathway ubiquitin-dependent protein catabolic process regulation of microtubule cytoskeleton organization Wnt signaling pathway proteolysis protein K63-linked deubiquitination regulation of mitotic cell cycle positive regulation of extrinsic apoptotic signaling pathway cell cycle negative regulation of type I interferon production negative regulation of NF-kappaB transcription factor activity nucleotide-binding oligomerization domain containing signaling pathway negative regulation of canonical Wnt signaling pathway immune system process regulation of tumor necrosis factor-mediated signaling pathway protein deubiquitination CD4-positive or CD8-positive, alpha-beta T cell lineage commitment regulation of protein binding innate immune response regulation of B cell differentiation negative regulation of T cell differentiation positive regulation of T cell differentiation homeostasis of number of cells positive regulation of T cell receptor signaling pathway necroptosis protein K48-linked deubiquitination ripoptosome assembly involved in necroptotic process regulation of cilium assembly positive regulation of protein localization protein linear deubiquitination cytoplasmic translation negative regulation of NIK/NF-kappaB signaling negative regulation of JNK cascade negative regulation of p38MAPK cascade regulation of inflammatory response regulation of necroptotic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1540 74256 Ensembl ENSG00000083799 ENSMUSG00000036712 UniProt Q9NQC7 Q80TQ2 RefSeq (mRNA) NM_001042355 NM_001042412 NM_015247 NM_001128169 NM_001128170 NM_001128171 NM_001276279 NM_173369 RefSeq (protein) NP_001035814 NP_001035877 NP_056062 NP_001365672 NP_001365673 NP_001365674 NP_001365675 NP_001365676 NP_001365677 NP_001365678 NP_001365679 NP_001365680 NP_001365681 NP_001365682 NP_001365683 NP_001365684 NP_001035814.1 NP_001035877.1 NP_001121642 NP_001121643 NP_001263208 NP_775545 Location (UCSC) Chr 16: 50.74 – 50.8 Mb Chr 8: 89.42 – 89.48 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

The CYLD gene in known to code for a cytoplasmic protein, termed CYLD lysine 63 deubiquitinase (here termed CYLD protein), which has three cytoskeletal-associated protein-glycine-conserved (CAP-GLY) domains (areas or the protein controlling critical functions). CYLD protein is a deubiquitinating enzyme, i.e. a protease that removes ubiquitin from certain proteins and thereby regulates these proteins' activities. CYLD protein removes ubiquitin from proteins involved in regulating the NF-κB, Wnt, notch, TGF-β, and JNK cell signaling pathways; these pathways normally act to regulate hair formation, cell growth, cell survival, inflammatory responses, and/or tumor development.

The CYLD gene is classified as a tumor suppressor gene, i.e. a gene that regulates cell growth and when inactivated by a mutation leads to uncontrolled cell growth and the formation of tumors. Inactivating mutations in this gene occur in essentially all cases of the CYLD cutaneous syndrome, a hereditary disorder in which individuals develop multiple skin tumors. The CYLD cutaneous syndrome includes three somewhat different forms of the disease: the multiple familial trichoepithelioma-type, Brooke–Spiegler syndrome-type, and familial cylindromatosis-type. CYLD gene mutations are also associated with T-Cell Acute Lymphoblastic Leukemia, multiple myeloma, hepatocellular carcinoma, neuroblastoma, pancreatic cancer, uterine cancer, stomach cancer, colon cancer, lung cancer, and human papillomavirus-associated cancers.

Further reading

• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (June 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research. 9 (3): 99–106. CiteSeerX 10.1.1.500.923. doi:10.1093/dnares/9.3.99. PMID 12168954.
• Lian F, Cockerell CJ (2006). "Cutaneous appendage tumors: familial cylindromatosis and associated tumors update". Advances in Dermatology. 21: 217–34. doi:10.1016/j.yadr.2005.06.005. PMID 16350444.
• Biggs PJ, Wooster R, Ford D, Chapman P, Mangion J, Quirk Y, Easton DF, Burn J, Stratton MR (December 1995). "Familial cylindromatosis (turban tumour syndrome) gene localised to chromosome 16q12-q13: evidence for its role as a tumour suppressor gene". Nature Genetics. 11 (4): 441–3. doi:10.1038/ng1295-441. PMID 7493027. S2CID 33637152.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Biggs PJ, Chapman P, Lakhani SR, Burn J, Stratton MR (March 1996). "The cylindromatosis gene (cyld1) on chromosome 16q may be the only tumour suppressor gene involved in the development of cylindromas". Oncogene. 12 (6): 1375–7. PMID 8649842.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (December 1998). "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (6): 355–64. doi:10.1093/dnares/5.6.355. PMID 10048485.
• Thomson SA, Rasmussen SA, Zhang J, Wallace MR (1999). "A new hereditary cylindromatosis family associated with CYLD1 on chromosome 16". Human Genetics. 105 (1–2): 171–3. doi:10.1007/s004399900077. PMID 10480375.
• Bignell GR, Warren W, Seal S, Takahashi M, Rapley E, Barfoot R, Green H, Brown C, Biggs PJ, Lakhani SR, Jones C, Hansen J, Blair E, Hofmann B, Siebert R, Turner G, Evans DG, Schrander-Stumpel C, Beemer FA, van Den Ouweland A, Halley D, Delpech B, Cleveland MG, Leigh I, Leisti J, Rasmussen S (June 2000). "Identification of the familial cylindromatosis tumour-suppressor gene". Nature Genetics. 25 (2): 160–5. doi:10.1038/76006. PMID 10835629. S2CID 22829077.
• Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (October 2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Research. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
• Trompouki E, Hatzivassiliou E, Tsichritzis T, Farmer H, Ashworth A, Mosialos G (August 2003). "CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members". Nature. 424 (6950): 793–6. Bibcode:2003Natur.424..793T. doi:10.1038/nature01803. hdl:21.11116/0000-0007-948F-1. PMID 12917689. S2CID 4424549.
• Brummelkamp TR, Nijman SM, Dirac AM, Bernards R (August 2003). "Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB". Nature. 424 (6950): 797–801. Bibcode:2003Natur.424..797B. doi:10.1038/nature01811. hdl:1874/17767. PMID 12917690. S2CID 4416878.
• Kovalenko A, Chable-Bessia C, Cantarella G, Israël A, Wallach D, Courtois G (August 2003). "The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination". Nature. 424 (6950): 801–5. Bibcode:2003Natur.424..801K. doi:10.1038/nature01802. PMID 12917691. S2CID 4397177.
• Hu G, Onder M, Gill M, Aksakal B, Oztas M, Gürer MA, Celebi JT (October 2003). "A novel missense mutation in CYLD in a family with Brooke-Spiegler syndrome". The Journal of Investigative Dermatology. 121 (4): 732–4. doi:10.1046/j.1523-1747.2003.12514.x. hdl:20.500.12648/7847. PMID 14632188.
• Regamey A, Hohl D, Liu JW, Roger T, Kogerman P, Toftgard R, Huber M (December 2003). "The tumor suppressor CYLD interacts with TRIP and regulates negatively nuclear factor kappaB activation by tumor necrosis factor". The Journal of Experimental Medicine. 198 (12): 1959–64. doi:10.1084/jem.20031187. PMC 2194148. PMID 14676304.
• Zhang XJ, Liang YH, He PP, Yang S, Wang HY, Chen JJ, Yuan WT, Xu SJ, Cui Y, Huang W (March 2004). "Identification of the cylindromatosis tumor-suppressor gene responsible for multiple familial trichoepithelioma". The Journal of Investigative Dermatology. 122 (3): 658–64. doi:10.1111/j.0022-202X.2004.22321.x. PMID 15086550.
• Jono H, Lim JH, Chen LF, Xu H, Trompouki E, Pan ZK, Mosialos G, Li JD (August 2004). "NF-kappaB is essential for induction of CYLD, the negative regulator of NF-kappaB: evidence for a novel inducible autoregulatory feedback pathway". The Journal of Biological Chemistry. 279 (35): 36171–4. doi:10.1074/jbc.M406638200. hdl:21.11116/0000-0007-9489-7. PMID 15226292.

External links

• Human CYLD genome location and CYLD gene details page in the UCSC Genome Browser.