RanBP-type and C3HC4-type zinc finger-containing protein 1 (also known as HOIL-1) is a protein that in humans is encoded by the RBCK1 gene.[5]
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RBCK1 |
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Identifiers |
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Aliases | RBCK1, C20orf18, HOIL-1, HOIL1, PBMEI, RBCK2, RNF54, UBCE7IP3, XAP3, XAP4, ZRANB4, PGBM1, RANBP2-type and C3HC4-type zinc finger containing 1 |
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External IDs | OMIM: 610924; MGI: 1344372; HomoloGene: 32448; GeneCards: RBCK1; OMA:RBCK1 - orthologs |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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Top expressed in | - right hemisphere of cerebellum
- anterior pituitary
- right uterine tube
- right lobe of liver
- granulocyte
- right adrenal gland
- left adrenal cortex
- right adrenal cortex
- right lobe of thyroid gland
- mucosa of transverse colon
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| Top expressed in | - neural layer of retina
- superior frontal gyrus
- ankle joint
- thymus
- lip
- dentate gyrus of hippocampal formation granule cell
- primary visual cortex
- granulocyte
- mesenteric lymph nodes
- genital tubercle
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BioGPS | |
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Wikidata |
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The protein encoded by this gene is similar to mouse UIP28/UbcM4 interacting protein. Alternative splicing has been observed at this locus, resulting in distinct isoforms.[5]
HOIL-1 is an E3 ubiquitin ligase and a part of the linear ubiquitin chain assembly complex (LUBAC), the only known ubiquitin ligase generating linear (Met1) polyubiquitin linkages.[6] Although HOIL-1 isn’t responsible for the linear ubiquitin generation, it is a necessary component of LUBAC and ensures its proper assembly and function.[7] Interestingly, unlike most E3 ubiquitin ligases, HOIL-1 is able to catalyze oxyester bond formation between the C-terminus of a ubiquitin monomer and Ser/Thr of a different protein. This recently discovered function of HOIL-1 has so far been described in the context of MyD88 signaling.[8] Additionally, a catalytically inactive mutant of HOIL-1 (HOIL-1C458S) led to prolonged IKK activation and increase of inflammatory cytokine production by cytotoxic T cells. The proposed mechanism is that the ester-linked ubiquitin chains limit the size of isopeptide-linked (K63 and/or M1) ubiquitin chains.[9]
A family quartet was found with two children, both affected with a previously unreported disease, characterized by progressive muscular weakness and cardiomyopathy, with normal intelligence. During the course of the study, one additional unrelated patient was found with a comparable phenotype. From whole-genome sequence data, RBCK1, a gene encoding an E3 ubiquitin-protein ligase, was identified as the most likely candidate gene, with two protein-truncating mutations in probands in the first family. Sanger sequencing identified a private homozygous splice variant in RBCK1 in the proband in the second family, yet single-nucleotide polymorphism (SNP) genotyping revealed a 1.2Mb copy-neutral region of homozygosity covering RBCK1. RNA-Seq confirmed aberrant splicing of RBCK1 transcripts, resulting in truncated protein products.[10] Ten other individuals with mutations in RBCK1 and overlapping phenotypes have been identified.[11]
Nilsson J, Schoser B, Laforet P, Kalev O, Lindberg C, Romero NB, et al. (December 2013). "Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1". Annals of Neurology. 74 (6): 914–919. doi:10.1002/ana.23963. PMID 23798481. S2CID 205344695.
- Martinez-Noel G, Niedenthal R, Tamura T, Harbers K (July 1999). "A family of structurally related RING finger proteins interacts specifically with the ubiquitin-conjugating enzyme UbcM4". FEBS Letters. 454 (3): 257–261. doi:10.1016/S0014-5793(99)00823-6. PMID 10431818. S2CID 46159115.
- Yamanaka K, Ishikawa H, Megumi Y, Tokunaga F, Kanie M, Rouault TA, et al. (April 2003). "Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2". Nature Cell Biology. 5 (4): 336–340. doi:10.1038/ncb952. PMID 12629548. S2CID 20453941.
- Hillman RT, Green RE, Brenner SE (2005). "An unappreciated role for RNA surveillance". Genome Biology. 5 (2): R8. doi:10.1186/gb-2004-5-2-r8. PMC 395752. PMID 14759258.
- Tatematsu K, Yoshimoto N, Koyanagi T, Tokunaga C, Tachibana T, Yoneda Y, et al. (June 2005). "Nuclear-cytoplasmic shuttling of a RING-IBR protein RBCK1 and its functional interaction with nuclear body proteins". The Journal of Biological Chemistry. 280 (24): 22937–22944. doi:10.1074/jbc.M413476200. PMID 15833741.
- Zhang Y, Wolf-Yadlin A, Ross PL, Pappin DJ, Rush J, Lauffenburger DA, White FM (September 2005). "Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules". Molecular & Cellular Proteomics. 4 (9): 1240–1250. doi:10.1074/mcp.M500089-MCP200. PMID 15951569.
- Yoshimoto N, Tatematsu K, Koyanagi T, Okajima T, Tanizawa K, Kuroda S (September 2005). "Cytoplasmic tethering of a RING protein RBCK1 by its splice variant lacking the RING domain". Biochemical and Biophysical Research Communications. 335 (2): 550–557. doi:10.1016/j.bbrc.2005.07.104. PMID 16083853.
- Bayle J, Lopez S, Iwaï K, Dubreuil P, De Sepulveda P (May 2006). "The E3 ubiquitin ligase HOIL-1 induces the polyubiquitination and degradation of SOCS6 associated proteins". FEBS Letters. 580 (11): 2609–2614. doi:10.1016/j.febslet.2006.03.093. PMID 16643902. S2CID 44648698.
- Tian Y, Zhang Y, Zhong B, Wang YY, Diao FC, Wang RP, et al. (June 2007). "RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-triggered NF-kappaB activation by targeting TAB2/3 for degradation". The Journal of Biological Chemistry. 282 (23): 16776–16782. doi:10.1074/jbc.M701913200. PMID 17449468.
- Wang K, Kim C, Bradfield J, Guo Y, Toskala E, Otieno FG, et al. (2013). "Whole-genome DNA/RNA sequencing identifies truncating mutations in RBCK1 in a novel Mendelian disease with neuromuscular and cardiac involvement". Genome Medicine. 5 (7): 67. doi:10.1186/gm471. PMC 3971341. PMID 23889995.