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
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2CRC, 2LGY, 4DBG
Identifiers
Aliases	RBCK1, C20orf18, HOIL-1, HOIL1, PBMEI, RBCK2, RNF54, UBCE7IP3, XAP3, XAP4, ZRANB4, PGBM1, RANBP2-type and C3HC4-type zinc finger containing 1
External IDs	OMIM: 610924; MGI: 1344372; HomoloGene: 32448; GeneCards: RBCK1; OMA:RBCK1 - orthologs
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20p13 Start 407,498 bp[1] End 432,139 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 G3 Start 152,158,254 bp[2] End 152,174,573 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) 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 Top expressed in superior frontal gyrus ankle joint thymus lip esophagus spleen crypt of lieberkuhn of small intestine neural tube cerebellar cortex duodenum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA-binding transcription factor activity metal ion binding ubiquitin binding protein binding ubiquitin-protein transferase activity transferase activity identical protein binding Cellular component cytosol LUBAC complex Biological process negative regulation of necroptotic process regulation of tumor necrosis factor-mediated signaling pathway positive regulation of NF-kappaB transcription factor activity positive regulation of apoptotic process positive regulation of I-kappaB kinase/NF-kappaB signaling positive regulation of extrinsic apoptotic signaling pathway viral process I-kappaB kinase/NF-kappaB signaling negative regulation of NF-kappaB transcription factor activity T cell receptor signaling pathway protein linear polyubiquitination proteasome-mediated ubiquitin-dependent protein catabolic process protein polyubiquitination positive regulation of NIK/NF-kappaB signaling regulation of transcription, DNA-templated Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10616 24105 Ensembl ENSG00000125826 ENSMUSG00000027466 UniProt Q9BYM8 Q9WUB0 RefSeq (mRNA) NM_006462 NM_031227 NM_031228 NM_031229 NM_001323956 NM_001323958 NM_001323960 NM_001083921 NM_019705 NM_001355282 RefSeq (protein) NP_001310885 NP_001310887 NP_001310889 NP_006453 NP_112506 NP_001077390 NP_062679 NP_001342211 Location (UCSC) Chr 20: 0.41 – 0.43 Mb Chr 2: 152.16 – 152.17 Mb PubMed search [3] [4]
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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-1^C458S) 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]