RBCK1

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. [provided by RefSeq]

Full Name

RanBP-type and C3HC4-type zinc finger containing 1

Function

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:21455173, PubMed:21455180, PubMed:21455181, PubMed:19136968).
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:21455173, PubMed:21455180, PubMed:21455181, PubMed:19136968).
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:21455173, PubMed:21455180, PubMed:21455181, PubMed:19136968).
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).

Biological Process

Biological Process cytoplasmic sequestering of proteinIDA:GO_Central
Biological Process defense response to bacteriumManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of necroptotic processIEA:Ensembl
Biological Process negative regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of extrinsic apoptotic signaling pathwayIEA:Ensembl
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of NIK/NF-kappaB signalingIEA:Ensembl
Biological Process proteasome-mediated ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process protein linear polyubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein polyubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process T cell receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

cytosol
LUBAC complex
ubiquitin ligase complex

Involvement in disease

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.

PTM

Auto-ubiquitinated. Auto-ubiquitination leads to degradation by the proteasome (By similarity).
Phosphorylated. In vitro, phosphorylation inhibits auto-ubiquitination activity (By similarity).