RBCK1

The RanBP2-type zinc finger, also called Npl4 zinc finger (NZF), mediates binding to 'Met-1'-linked polyubiquitins.

The UBL domain mediates association with RNF31 via interaction with its UBA domain.

E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, such as UBE2L3/UBCM4, and then transfers it to substrates (PubMed:12629548, PubMed:17449468, PubMed:18711448). Functions as an E3 ligase for oxidized IREB2 and both heme and oxygen are necessary for IREB2 ubiquitination (PubMed:12629548). Promotes ubiquitination of TAB2 and IRF3 and their degradation by the proteasome (PubMed:17449468, PubMed:18711448). Component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation (PubMed:17006537, PubMed:19136968, PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways (PubMed:17006537, PubMed:19136968, PubMed:21455173, PubMed:21455180, PubMed:21455181). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (PubMed:17006537, PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex (PubMed:17006537, PubMed:19136968, PubMed:21455173, PubMed:21455180, PubMed:21455181). The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria (PubMed:28481331). LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin (PubMed:28481331). The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation (PubMed:28481331). Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (PubMed:23708998). Binds polyubiquitin of different linkage types (PubMed:20005846, PubMed:21455181).

Polyglucosan body myopathy 1 with or without immunodeficiency

PGBM1

A disease characterized by polyglucosan storage myopathy associated with early-onset progressive muscle weakness and progressive dilated cardiomyopathy, which may necessitate cardiac transplant in severe cases. Some patients present with severe immunodeficiency, invasive bacterial infections and chronic autoinflammation.

None

The disease is caused by variants affecting the gene represented in this entry.

Protein modification; protein ubiquitination.

Auto-ubiquitinated. Auto-ubiquitination leads to degradation by the proteasome (By similarity).

Phosphorylated. In vitro, phosphorylation inhibits auto-ubiquitination activity (By similarity).

(Microbial infection) Ubiquitinated by S.flexneri E3 ubiquitin-protein ligases IpaH1.4 and IpaH2.5, leading to its degradation by the proteasome, thereby preventing formation of the bacterial ubiquitin coat and activation of innate immunity (PubMed:27572974, PubMed:35294289).

Belongs to the RBR family.

C20orf18, RNF54, UBCE7IP3, XAP3, XAP4, RBCK1, RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, Heme-oxidized IRP2 ubiquitin ligase 1, Hepatitis B virus X-associated protein 4, RING finger protein 54, RING-type E3 ubiquitin transferase HOIL-1, Ubiquitin-conjugating enzyme 7-interacting protein 3, HOIL-1

• entrezGene:10616
• omim:610924
• swissprot:Q9BYM8

Proteins

Neuroscience

57572Da